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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 1 - 200 of 253 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 29)
AAPS Open     Open Access   (Followers: 5)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
AboutOpen     Open Access  
ACS Pharmacology & Translational Science     Hybrid Journal   (Followers: 3)
Acta Pharmaceutica     Open Access   (Followers: 4)
Acta Pharmaceutica Indonesia     Open Access  
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Pharmacologica Sinica     Hybrid Journal   (Followers: 2)
Acta Physiologica Hungarica     Full-text available via subscription  
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 4)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 95)
Advanced Therapeutics     Hybrid Journal   (Followers: 1)
Advances in Medical, Pharmaceutical and Dental Research     Open Access   (Followers: 14)
Advances in Pharmacological and Pharmaceutical Sciences     Open Access   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15)
Advances in Pharmacology and Pharmacy     Open Access   (Followers: 7)
Advances in Traditional Medicine     Hybrid Journal   (Followers: 5)
Adverse Drug Reaction Bulletin     Full-text available via subscription   (Followers: 4)
AJP : The Australian Journal of Pharmacy     Full-text available via subscription   (Followers: 11)
Al-Azhar Journal of Pharmaceutical Sciences     Open Access   (Followers: 6)
Alternatives to Laboratory Animals     Full-text available via subscription   (Followers: 6)
American Journal of Cardiovascular Drugs     Hybrid Journal   (Followers: 20)
American Journal of Drug Discovery and Development     Open Access   (Followers: 3)
American Journal of Health-System Pharmacy     Full-text available via subscription   (Followers: 51)
American Journal of Pharmacology and Toxicology     Open Access   (Followers: 21)
American Journal of Therapeutics     Hybrid Journal   (Followers: 11)
Analytical Methods     Hybrid Journal   (Followers: 7)
Annales Pharmaceutiques Francaises     Full-text available via subscription   (Followers: 1)
Annals of Pharmacotherapy     Hybrid Journal   (Followers: 52)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 27)
Anti-Infective Agents     Hybrid Journal   (Followers: 5)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 6)
Antibiotics     Open Access   (Followers: 12)
Antibody Therapeutics     Open Access  
Antiviral Chemistry and Chemotherapy     Open Access   (Followers: 1)
Antiviral Research     Hybrid Journal   (Followers: 7)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Pharmacal Research     Full-text available via subscription   (Followers: 1)
Archives of Pharmacy and Pharmaceutical Sciences     Open Access   (Followers: 2)
Archives of Razi Institute     Open Access   (Followers: 1)
Archivos Venezolanos de Farmacología y Terapéutica     Open Access  
Ars Pharmaceutica     Open Access  
Asian Journal of Medical and Pharmaceutical Researches     Open Access  
Asian Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
Asian Journal of Research in Medical and Pharmaceutical Sciences     Open Access  
ASSAY and Drug Development Technologies     Hybrid Journal   (Followers: 4)
Australian Journal of Herbal Medicine     Full-text available via subscription   (Followers: 4)
Australian Pharmacist     Full-text available via subscription   (Followers: 7)
Autonomic & Autacoid Pharmacology     Hybrid Journal  
Avicenna Journal of Phytomedicine     Open Access   (Followers: 1)
Bangladesh Journal of Pharmacology     Open Access  
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11)
Behavioural Pharmacology     Hybrid Journal   (Followers: 2)
Biochemical Pharmacology     Hybrid Journal   (Followers: 9)
BioDrugs     Full-text available via subscription   (Followers: 4)
Biomaterials     Hybrid Journal   (Followers: 54)
Biomedical and Environmental Sciences     Full-text available via subscription   (Followers: 1)
Biomedicine & Pharmacotherapy     Full-text available via subscription   (Followers: 2)
Biometrical Journal     Hybrid Journal   (Followers: 6)
Biopharm International     Full-text available via subscription   (Followers: 8)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 12)
BMC Pharmacology     Open Access   (Followers: 3)
BMC Pharmacology & Toxicology     Open Access   (Followers: 5)
British Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 25)
British Journal of Pharmacology     Hybrid Journal   (Followers: 14)
British Journal of Pharmacy (BJPharm)     Open Access   (Followers: 2)
Bulletin of Faculty of Pharmacy, Cairo University     Open Access   (Followers: 2)
CADTH Technology Overviews     Free  
Canadian Journal of Pain     Open Access   (Followers: 3)
Canadian Journal of Physiology and Pharmacology     Hybrid Journal   (Followers: 1)
Canadian Pharmacists Journal / Revue des Pharmaciens du Canada     Hybrid Journal   (Followers: 3)
Cancer Biotherapy & Radiopharmaceuticals     Hybrid Journal  
Cancer Chemotherapy and Pharmacology     Hybrid Journal   (Followers: 4)
Cardiovascular Drugs and Therapy     Hybrid Journal   (Followers: 12)
Cardiovascular Therapeutics     Open Access   (Followers: 3)
Cephalalgia Reports     Open Access  
Chemical Research in Toxicology     Hybrid Journal   (Followers: 20)
ChemMedChem     Hybrid Journal   (Followers: 9)
Chinese Herbal Medicines     Full-text available via subscription   (Followers: 1)
Chinese Journal of Pharmaceutical Analysis     Full-text available via subscription  
Clinical and Experimental Pharmacology and Physiology     Hybrid Journal   (Followers: 3)
Clinical and Translational Science     Open Access   (Followers: 4)
Clinical Complementary Medicine and Pharmacology     Open Access   (Followers: 1)
Clinical Drug Investigation     Full-text available via subscription   (Followers: 6)
Clinical Medicine Insights : Therapeutics     Open Access  
Clinical Neuropharmacology     Hybrid Journal   (Followers: 2)
Clinical Pharmacist     Partially Free   (Followers: 11)
Clinical Pharmacokinetics     Full-text available via subscription   (Followers: 16)
Clinical Pharmacology & Therapeutics     Hybrid Journal   (Followers: 31)
Clinical Pharmacology in Drug Development     Hybrid Journal   (Followers: 2)
Clinical Pharmacology: Advances and Applications     Open Access   (Followers: 5)
Clinical Research and Regulatory Affairs     Hybrid Journal   (Followers: 5)
Clinical Therapeutics     Hybrid Journal   (Followers: 10)
Clinical Toxicology     Hybrid Journal   (Followers: 17)
Clinical Trials     Hybrid Journal   (Followers: 12)
CNS Drug Reviews     Open Access   (Followers: 3)
CNS Drugs     Full-text available via subscription   (Followers: 10)
Combination Products in Therapy     Open Access  
Consultant Pharmacist     Full-text available via subscription   (Followers: 2)
Consumer Drugs     Full-text available via subscription  
Contract Pharma     Full-text available via subscription  
Cosmetics     Open Access   (Followers: 4)
CPT : Pharmacometrics & Systems Pharmacology     Open Access   (Followers: 6)
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 16)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 22)
Current Bioactive Compounds     Hybrid Journal  
Current Cancer Therapy Reviews     Hybrid Journal   (Followers: 5)
Current Clinical Pharmacology     Hybrid Journal   (Followers: 3)
Current Drug Delivery     Hybrid Journal   (Followers: 6)
Current Drug Discovery Technologies     Hybrid Journal   (Followers: 5)
Current Drug Metabolism     Hybrid Journal   (Followers: 3)
Current Drug Safety     Hybrid Journal   (Followers: 8)
Current Drug Targets     Hybrid Journal   (Followers: 2)
Current Drug Therapy     Hybrid Journal   (Followers: 2)
Current Enzyme Inhibition     Hybrid Journal   (Followers: 2)
Current Issues in Pharmacy and Medical Sciences     Open Access   (Followers: 2)
Current Medical Science     Hybrid Journal  
Current Medicinal Chemistry     Hybrid Journal   (Followers: 7)
Current Molecular Pharmacology     Hybrid Journal  
Current Nanoscience     Hybrid Journal  
Current Neuropharmacology     Hybrid Journal   (Followers: 1)
Current Opinion in Pharmacology     Hybrid Journal   (Followers: 8)
Current Pharmaceutical Analysis     Hybrid Journal   (Followers: 1)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 8)
Current Pharmaceutical Design     Hybrid Journal   (Followers: 4)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Current Pharmacology Reports     Hybrid Journal  
Current Protocols in Pharmacology     Hybrid Journal  
Current Radiopharmaceuticals     Hybrid Journal   (Followers: 1)
Current Research in Drug Discovery     Open Access   (Followers: 1)
Current Research in Pharmacology and Drug Discovery     Open Access   (Followers: 6)
Current Therapeutic Research     Open Access   (Followers: 5)
Current trends in Biotechnology and Pharmacy     Open Access   (Followers: 7)
Current Vascular Pharmacology     Hybrid Journal   (Followers: 1)
Dhaka University Journal of Pharmaceutical Sciences     Open Access  
Die Pharmazie - An International Journal of Pharmaceutical Sciences     Full-text available via subscription   (Followers: 3)
Dose-Response     Open Access  
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 12)
Drug and Therapeutics Bulletin     Hybrid Journal   (Followers: 8)
Drug Delivery     Open Access   (Followers: 7)
Drug Delivery and Translational Research     Hybrid Journal   (Followers: 2)
Drug Design, Development and Therapy     Open Access   (Followers: 1)
Drug Development and Industrial Pharmacy     Hybrid Journal   (Followers: 25)
Drug Development Research     Hybrid Journal   (Followers: 8)
Drug Discovery Today     Full-text available via subscription   (Followers: 63)
Drug Metabolism and Disposition     Hybrid Journal   (Followers: 9)
Drug Metabolism and Pharmacokinetics     Hybrid Journal   (Followers: 4)
Drug Metabolism Letters     Hybrid Journal   (Followers: 2)
Drug Metabolism Reviews     Hybrid Journal   (Followers: 3)
Drug Research     Hybrid Journal   (Followers: 1)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
Drug Safety     Full-text available via subscription   (Followers: 81)
Drug Safety - Case Reports     Open Access   (Followers: 2)
Drug Target Insights     Open Access  
Drug, Healthcare and Patient Safety     Open Access   (Followers: 8)
Drugs     Full-text available via subscription   (Followers: 146)
Drugs & Aging     Full-text available via subscription   (Followers: 9)
Drugs & Therapy Perspectives     Full-text available via subscription   (Followers: 9)
Drugs : Real World Outcomes     Hybrid Journal   (Followers: 1)
Drugs in R & D     Full-text available via subscription   (Followers: 2)
Drugs of the Future     Full-text available via subscription   (Followers: 4)
East and Central African Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
EJNMMI Radiopharmacy and Chemistry     Open Access  
EMC - Cosmetologia Medica e Medicina degli Inestetismi Cutanei     Full-text available via subscription  
Emerging Trends in Drugs, Addictions, and Health     Open Access   (Followers: 2)
Environmental Toxicology and Pharmacology     Hybrid Journal   (Followers: 7)
Epilepsy Research     Hybrid Journal   (Followers: 8)
Ethiopian Pharmaceutical Journal     Full-text available via subscription   (Followers: 1)
EUREKA : Health Sciences     Open Access  
European Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 11)
European Journal of Drug Metabolism and Pharmacokinetics     Hybrid Journal   (Followers: 5)
European Journal of Hospital Pharmacy : Science and Practice (EJHP)     Hybrid Journal   (Followers: 5)
European Journal of Medicinal Plants     Open Access   (Followers: 2)
European Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 84)
European Journal of Pharmaceutics and Biopharmaceutics     Hybrid Journal   (Followers: 23)
European Journal of Pharmacology     Hybrid Journal   (Followers: 3)
European Medical, Health and Pharmaceutical Journal     Open Access   (Followers: 2)
European Neuropsychopharmacology     Hybrid Journal   (Followers: 8)
European Pharmaceutical Journal     Open Access  
European Review for Medical and Pharmacological Sciences     Full-text available via subscription   (Followers: 1)
Experimental and Clinical Psychopharmacology     Full-text available via subscription   (Followers: 7)
Expert Opinion on Drug Delivery     Hybrid Journal   (Followers: 18)
Expert Opinion on Drug Discovery     Hybrid Journal   (Followers: 16)
Expert Opinion on Emerging Drugs     Hybrid Journal   (Followers: 7)
Expert Opinion on Investigational Drugs     Hybrid Journal   (Followers: 10)
Expert Opinion on Orphan Drugs     Hybrid Journal  
Expert Opinion on Pharmacotherapy     Hybrid Journal   (Followers: 7)
Expert Review of Anti-infective Therapy     Full-text available via subscription   (Followers: 5)
Expert Review of Cardiovascular Therapy     Full-text available via subscription   (Followers: 4)
Expert Review of Clinical Pharmacology     Hybrid Journal   (Followers: 2)
Expert Review of Molecular Diagnostics     Full-text available via subscription   (Followers: 5)
Expert Review of Pharmacoeconomics & Outcomes Research     Full-text available via subscription   (Followers: 6)
Expert Review of Precision Medicine and Drug Development     Hybrid Journal   (Followers: 4)
Exploratory Research in Clinical and Social Pharmacy     Open Access   (Followers: 4)
Fitoterapia     Hybrid Journal   (Followers: 5)
Food Additives & Contaminants Part A     Hybrid Journal   (Followers: 8)
Frontiers in Drug Design & Discovery     Hybrid Journal   (Followers: 7)
Frontiers in Medical Technology     Open Access  

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Journal Cover
Clinical Pharmacokinetics
Journal Prestige (SJR): 1.482
Citation Impact (citeScore): 4
Number of Followers: 16  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 0312-5963 - ISSN (Online) 1179-1926
Published by Adis Homepage  [21 journals]
  • Evaluating the Clinical Impact and Feasibility of Therapeutic Drug
           Monitoring of Pazopanib in a Real-World Soft-Tissue Sarcoma Cohort

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      Abstract: Introduction and Objective Pazopanib is registered for metastatic renal cell carcinoma and soft-tissue sarcoma (STS). Its variable pharmacokinetic (PK) characteristics and narrow therapeutic range provide a strong rationale for therapeutic drug monitoring (TDM). Prior studies have defined target levels of drug exposure (≥ 20.5 mg/L) linked to prolonged progression-free survival (PFS), but the added value of using TDM remains unclear. This study investigates the effect of TDM of pazopanib in patients with STS on survival outcomes and dose-limiting toxicities (DLTs) and evaluates the feasibility of TDM-guided dosing. Methods A TDM-guided cohort was compared to a non-TDM-guided cohort for PFS, overall survival (OS) and DLTs. PK samples were available from all patients, though not acted upon in the non-TDM-guided cohort. We evaluated the feasibility of TDM by comparing the proportion of underdosed patients in our TDM cohort with data from previous publications. Results A total of 122 STS patients were included in the TDM-guided cohort (n = 95) and non-TDM-guided cohort (n = 27). The average exposure in the overall population was 30.5 mg/L and was similar in both groups. Median PFS and OS did not differ between the TDM-guided cohort and non-TDM-guided cohort (respectively 5.5 vs 4.4 months, p = 0.3, and 12.6 vs 10.1 months, p = 0.8). Slightly more patients in the non-TDM-guided cohort experienced DLTs (54%) compared to the TDM-guided cohort (44%). The proportion of underdosed patients (13.3%) was halved compared to historical data (26.7%). Conclusion TDM reduced the proportion of patients with subtherapeutic exposure levels by ~ 50%. Nonetheless, the added value of TDM for achieving target trough levels of ≥ 20.5 mg/L for pazopanib on survival outcomes could not be confirmed in STS patients.
      PubDate: 2024-07-16
       
  • Clinical Pharmacokinetics and Pharmacodynamics of Letermovir in Allogenic
           Hematopoietic Cell Transplantation

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      Abstract: Abstract Letermovir is a newly developed antiviral agent used for the prophylaxis of human cytomegalovirus infections in patients undergoing allogeneic hematopoietic cell transplantation. This novel anti-cytomegalovirus drug, used for the prophylaxis of cytomegalovirus reactivation until approximately 200 days after transplantation, effectively reduces the risk of clinically significant cytomegalovirus infection. No human counterpart exists for the terminase complex; letermovir is virus specific and lacks some toxicities previously observed with other anti-cytomegalovirus drugs, such as cytopenia and nephrotoxicity. The absolute bioavailability of letermovir in healthy individuals is estimated to be 94% based on a population-pharmacokinetic analysis. In contrast, oral administration of letermovir to patients undergoing hematopoietic cell transplantation results in lower exposure than that in healthy individuals. Renal or hepatic impairment does not influence the intrinsic clearance of letermovir. Co-administration of letermovir may alter the plasma concentrations of other drugs, including itself, as it acts as a substrate and inhibitor/inducer of several drug-metabolizing enzymes and transporters. In particular, attention should be paid to the drug–drug interactions between letermovir and calcineurin inhibitors or azole antifungal agents, which are commonly used in patients undergoing hematopoietic cell transplantation. This article reviews and summarizes the clinical pharmacokinetics and pharmacodynamics of letermovir, focusing on patients undergoing hematopoietic cell transplantation, healthy individuals, and specific patient subsets.
      PubDate: 2024-07-16
       
  • Can we Predict Drug Excretion into Saliva' A Systematic Review and
           Analysis of Physicochemical Properties

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      Abstract: Background and Objectives Saliva is a patient-friendly matrix for therapeutic drug monitoring (TDM) but is infrequently used in routine care. This is due to the uncertainty of saliva-based TDM results to inform dosing. This study aimed to retrieve data on saliva–plasma concentration and subsequently determine the physicochemical properties that influence the excretion of drugs into saliva to increase the foundational knowledge underpinning saliva-based TDM. Methods Medline, Web of Science and Embase (1974–2023) were searched for human clinical studies, which determined drug pharmacokinetics in both saliva and plasma. Studies with at least ten subjects and five paired saliva–plasma concentrations per subject were included. For each study, the ratio of the area under the concentration–time curve between saliva and plasma was determined to assess excretion into saliva. Physicochemical properties of each drug (e.g. pKa, lipophilicity, molecular weight, polar surface area, rotatable bonds and fraction of drug unbound to plasma proteins) were obtained from PubChem and Drugbank. Drugs were categorised by their ionisability, after which saliva-to-plasma ratios were predicted with adjustment for protein binding and physiological pH via the Henderson–Hasselbalch equation. Spearman correlation analyses were performed for each drug category to identify factors predicting saliva excretion (α = 5%). Study quality was assessed by the risk of bias in non-randomised studies of interventions tool. Results Overall, 42 studies including 40 drugs (anti-psychotics, anti-microbials, immunosuppressants, anti-thrombotic, anti-cancer and cardiac drugs) were included. The median saliva-to-plasma ratios were similar for drugs in the amphoteric (0.59), basic (0.43) and acidic (0.41) groups and lowest for drugs in the neutral group (0.21). Higher excretion of acidic drugs (n = 5) into saliva was associated with lower ionisation and protein binding (correlation between predicted versus observed saliva-to-plasma ratios: R2 = 0.85, p = 0.02). For basic drugs (n = 21), pKa predicted saliva excretion (Spearman correlation coefficient: R = 0.53, p = 0.02). For amphoteric drugs (n = 10), hydrogen bond donor (R = − 0.76, p = 0.01) and polar surface area (R = − 0.69, p = 0.02) were predictors. For neutral drugs (n = 10), protein binding (R = 0.84, p = 0.004), lipophilicity (R = − 0.65, p = 0.04) and hydrogen bond donor count (R = − 0.68, p = 0.03) were predictors. Drugs considered potentially suitable for saliva-based TDM are phenytoin, tacrolimus, voriconazole and lamotrigine. The studies had a low-to-moderate risk of bias. Conclusions Many commonly used drugs are excreted into saliva, which can be partly predicted by a drug’s ionisation state, protein binding, lipophilicity, hydrogen bond donor count and polar surface area. The contribution of drug transporters and physiological factors to the excretion needs to be evaluated. Continued research on drugs potentially suitable for saliva-based TDM will aid in adopting this person-centred TDM approach to improve patient outcomes.
      PubDate: 2024-07-15
       
  • Machine Learning Approach in Dosage Individualization of Isoniazid for
           Tuberculosis

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      Abstract: Introduction Isoniazid is a first-line antituberculosis agent with high variability, which would profit from individualized dosing. Concentrations of isoniazid at 2 h (C2h), as an indicator of safety and efficacy, are important for optimizing therapy. Objective The objective of this study was to establish machine learning (ML) models to predict the C2h, that can be used for establishing an individualized dosing regimen in clinical practice. Methods Published population pharmacokinetic (PopPK) models for adults were searched based on PubMed and ultimately four reliable models were selected for simulating individual C2h datasets under different conditions (demographics, genotype, ethnicity, etc.). Machine learning models were trained on simulated C2h obtained from the four PopPK models. Five different algorithms were used for ML model building to predict C2h. Real-world data were used for predictive performance evaluations. Virtual trials were used to compare ML-optimized doses with PopPK model-optimized doses. Results Categorical boosting (CatBoost) exhibited the highest prediction ability. Target C2h can be predicted using the ML model combined with the dosing regimen and three covariates (N-acetyltransferase 2 [NAT2] genotypes, weight and race [Asians and Africans]). Real-world data validation results showed that the ML model can achieve an overall prediction accuracy of 93.4%. Using the final ML model, the mean absolute prediction error value decreased by 45.7% relative to the average of PopPK models. Using the ML-optimized dosing regimen, the probability of target attainment increased by 43.7% relative to the PopPK model-optimized dosing regimens. Conclusion Machine learning models were developed with great predictive performance, which can be used to determine the individualized initial dose of isoniazid in adult patients.
      PubDate: 2024-07-11
       
  • Investigating the Bioavailability and Insulin-like Growth Factor-I Release
           of Two Different Strengths of Somapacitan: A Randomised, Double-Blind
           Crossover Trial

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      Abstract: Study Design and Objective Randomised, double-blind, crossover trial to confirm bioequivalence of somapacitan, a long-acting growth hormone (GH), in 5 mg/1.5 mL and 10 mg/1.5 mL strengths in equimolar doses. Methods Healthy participants were randomised (1:1:1) to subcutaneous somapacitan treatment in one dosing period with 5 mg/1.5 mL and two periods with 10 mg/1.5 mL. Eligibility criteria included age 18–45 years and body mass index 18.5–24.9 kg/m2. Exclusion criteria included history of GH deficiency, previous GH treatment, weight > 100.0 kg and participation in any clinical trial of an investigational medicinal product within 45 days or five times the half-life of the previous investigational product before screening. Area under the curve from time 0 until last quantifiable observation (AUC0–t), maximum serum concentration (Cmax), time to Cmax and terminal half-life of somapacitan and safety were assessed. Results In total, 33 participants were randomised. For AUC0–t, estimated treatment ratio (ETR) (5 mg/1.5 mL versus 10 mg/1.5 mL) was 0.95 (90% confidence interval [CI] 0.89–1.01). Point estimate and 90% CIs were within the acceptance range (0.80–1.25). For Cmax, ETR was 0.77 (90% CI 0.68–0.89). Point estimate and 90% CIs were outside the acceptance range (0.80–1.25). Mean insulin-like growth factor-I (IGF-I) and IGF-I standard deviation score concentration–time curves for each strength were almost identical. No new safety issues were identified. Conclusions Bioequivalence criterion for somapacitan 5 mg/1.5 mL and 10 mg/1.5 mL was met for AUC0–t but not for Cmax. The two strengths had equivalent IGF-I responses. Trial Registration ClinicalTrials.gov, NCT03905850 (3 April 2019).
      PubDate: 2024-07-05
       
  • Intra-individual Dose Escalation of Abiraterone According to Its Plasma
           Exposure in Patients with Progressive Metastatic Castration-Resistant
           Prostate Cancer: Results of the OPTIMABI Trial

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      Abstract: Background and Objective Trough abiraterone concentration (ABI Cmin) of 8.4 ng/mL has been identified as an appropriate efficacy threshold in patients treated for metastatic castration-resistant prostate cancer (mCRPC). The aim of the phase II OPTIMABI study was to evaluate the efficacy of pharmacokinetics (PK)-guided dose escalation of abiraterone acetate (AA) in underexposed patients with mCRPC with early tumour progression. Methods This multicentre, non-randomised study consisted of two sequential steps. In step 1, all patients started treatment with 1000 mg of AA once daily. Abiraterone Cmin was measured 22–26 h after the last dose intake each month during the first 12 weeks of treatment. In step 2, underexposed patients (Cmin < 8.4 ng/mL) with tumour progression within the first 6 months of treatment were enrolled and received AA 1000 mg twice daily. The primary endpoint was the rate of non-progression at 12 weeks after the dose doubling. During step 1, adherence to ABI treatment was assessed using the Girerd self-reported questionnaire. A post-hoc analysis of pharmacokinetic (PK) data was conducted using Bayesian estimation of Cmin from samples collected outside the sampling guidelines (22–26 h). Results In the intention-to-treat analysis (ITT), 81 patients were included in step 1. In all, 21 (26%) patients were underexposed in step 1, and 8 of them (38%) experienced tumour progression within the first 6 months. A total of 71 patients (88%) completed the Girerd self-reported questionnaire. Of the patients, 62% had a score of 0, and 38% had a score of 1 or 2 (minimal compliance failure), without a significant difference in mean ABI Cmin in the two groups. Four patients were enrolled in step 2, and all reached the exposure target (Cmin > 8.4 ng/mL) after doubling the dose, but none met the primary endpoint. In the post-hoc analysis of PK data, 32 patients (39%) were underexposed, and ABI Cmin was independently associated with worse progression-free survival [hazard ratio (HR) 2.50, 95% confidence interval (CI) 1.07–5.81; p = 0.03], in contrast to the ITT analysis. Conclusion The ITT and per-protocol analyses showed no statistical association between ABI underexposure and an increased risk of early tumour progression in patients with mCRPC, while the Bayesian estimator showed an association. However, other strategies than dose escalation at the time of progression need to be evaluated. Treatment adherence appeared to be uniformly good in the present study. Finally, the use of a Bayesian approach to recover samples collected outside the predefined blood collection time window could benefit the conduct of clinical trials based on drug monitoring. OPTIMABI trial is registered as National Clinical Trial number NCT03458247, with the EudraCT number 2017-000560-15)
      PubDate: 2024-07-04
       
  • Penetration of Antibiotics into Subcutaneous and Intramuscular
           Interstitial Fluid: A Meta-Analysis of Microdialysis Studies in Adults

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      Abstract: Background and Objective The interstitial fluid of tissues is the effect site for antibiotics targeting extracellular pathogens. Microdialysis studies investigating these concentrations in muscle and subcutaneous tissue have reported notable variability in tissue penetration. This study aimed to comprehensively summarise the existing data on interstitial fluid penetration in these tissues and to identify potential factors influencing antibiotic distribution. Methods A literature review was conducted, focusing on subcutaneous and intramuscular microdialysis studies of antibiotics in both adult healthy volunteers and patients. Random-effect meta-analyses were used to aggregate effect size estimates of tissue penetration. The primary parameter of interest was the unbound penetration ratio, which represents the ratio of the area under the concentration–time curve in interstitial fluid relative to the area under the concentration–time curve in plasma, using unbound concentrations. Results In total, 52 reports were incorporated into this analysis. The unbound antibiotic exposure in the interstitial fluid of healthy volunteers was, on average, 22% lower than in plasma. The unbound penetration ratio values were higher after multiple dosing but did not significantly differ between muscle and subcutaneous tissue. Unbound penetration ratio values were lower for acids and bases compared with neutral antibiotics. Neither the molecular weight nor the logP of the antibiotics accounted for the variations in the unbound penetration ratio. Obesity was associated with lower interstitial fluid penetration. Conditions such as sepsis, tissue inflammation and tissue ischaemia were not significantly associated with altered interstitial fluid penetration. Conclusions This study highlights the variability and generally lower exposure of unbound antibiotics in the subcutaneous and intramuscular interstitial fluid compared with exposure in plasma. Future research should focus on understanding the therapeutic relevance of these differences and identify key covariates that may influence them.
      PubDate: 2024-07-02
       
  • Characterizing Enoxaparin’s Population Pharmacokinetics to Guide Dose
           Individualization in the Pediatric Population

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      Abstract: Background and Objective Pediatric dosing of enoxaparin was derived based on extrapolation of the adult therapeutic range to children. However, a large fraction of children do not achieve therapeutic anticoagulation with initial dosing. We aim to use real-world anti-Xa data obtained from children receiving enoxaparin per standard of care to characterize the population pharmacokinetics (PopPK).Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct.The author names are accurately presented and the metadata are correct.  Methods A PopPK analysis was performed using NONMEM, and a stepwise covariate modeling approach was applied for the covariate selection. The final PopPK model, developed with data from 1293 patients ranging in age from 1 day to 18 years, was used to simulate enoxaparin subcutaneous dosing for prophylaxis and treatment based on total body weight (0–18 years, TBW) or fat-free mass (2–18 years, FFM). Simulated exposures in children with obesity (body mass index percentile ≥95th percentile) were compared with those without obesity. Results A linear, one-compartment PopPK model that included allometric scaling using TBW (<2 years) or FFM (≥2 years) characterized the enoxaparin pharmacokinetic data. In addition, serum creatinine was identified as a significant covariate influencing clearance. Simulations indicated that in patients aged <2 years, the recommended 1.5 mg/kg TBW-based dosing achieves therapeutic simulated concentrations. In pediatric patients aged ≥2 years, the recommended 1.0 mg/kg dose resulted in exposures more comparable in children with and without obesity when FFM weight-based dosing was applied. Conclusion Using real-world data and PopPK modeling, enoxaparin’s pharmacokinetics were characterized in pediatric patients. Using FFM and twice-daily dosing might reduce the risk of overdosing, especially in children with obesity.
      PubDate: 2024-07-02
       
  • The OCT2/MATE1 Interaction Between Trifluridine, Metformin and Cimetidine:
           A Crossover Pharmacokinetic Study

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      Abstract: Background and Objectives Trifluridine/tipiracil, registered for the treatment of patients with metastatic gastric and colorectal cancer, is a substrate and inhibitor for the organic cation transporter 2 (OCT2) and the multidrug and toxin extrusion protein 1 (MATE1), which raises the potential for drug–drug interactions with other OCT2/MATE1 modulators. Therefore, we prospectively examined the effect of an OCT2/MATE1 inhibitor (cimetidine) and substrate (metformin) on the pharmacokinetics of trifluridine. Methods In this three-phase crossover study, patients with metastatic colorectal or gastric cancer were sequentially treated with trifluridine/tipiracil alone (phase A), trifluridine/tipiracil concomitant with metformin (phase B) and trifluridine/tipiracil concomitant with cimetidine (phase C). The primary endpoint was the relative difference in exposure of trifluridine assessed by the area under the curve from timepoint zero to infinity. A > 30% change in exposure was considered clinically relevant. A p-value of < 0.025 was considered significant because of a Bonferroni correction. Results Eighteen patients were included in the analysis. Metformin did not significantly alter the exposure to trifluridine (− 12.6%; 97.5% confidence interval − 25.0, 1.8; p = 0.045). Cimetidine did alter the exposure to trifluridine significantly (+ 18.0%; 97.5% confidence interval 4.5, 33.3; p = 0.004), but this increase did not meet our threshold for clinical relevance. Metformin trough concentrations were not influenced by trifluridine/tipiracil. Conclusions Our result suggests that the OCT2/MATE1 modulators cimetidine and metformin can be co-administered with trifluridine/tipiracil without clinically relevant effects on drug exposure. Clinical Trial Registration NL8067 (registered 04-10-2019).
      PubDate: 2024-06-28
       
  • Correction to: Hyperinflammation Reduces Midazolam Metabolism in
           Critically Ill Adults with COVID‑19

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      PubDate: 2024-06-28
       
  • Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric
           Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results
           of Study ITCC-059

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      Abstract: Background and Objective Inotuzumab ozogamicin is an antibody-drug conjugate approved for treating relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in adults. Pediatric pharmacokinetic data of inotuzumab ozogamicin are lacking. This study is the first to examine the population pharmacokinetics of inotuzumab ozogamicin in pediatric patients with relapsed/refractory BCP-ALL. Methods From 531 adult patients with B-cell non-Hodgkin’s lymphoma, 234 adult patients with BCP-ALL, and 53 pediatric patients with BCP-ALL, 8924 inotuzumab ozogamicin serum concentrations were analyzed using non-linear mixed-effects modeling. A published adult inotuzumab ozogamicin population-pharmacokinetic model, a two-compartment model with linear and time-dependent clearance, was adapted to describe the pediatric data. Results Modifications in this analysis, compared to the published adult model, included: (i) re-estimating pharmacokinetic parameters and covariate effects; (ii) modifying covariate representation; and (iii) introducing relevant pediatric covariate effects (age on the decay coefficient of time-dependent clearance and ALL effect (disease type and/or different bioanalytical analysis methods) on initial values of time-dependent clearance). For patients with relapsed/refractory BCP-ALL, increasing age was associated with a decreasing decay coefficient of time-dependent clearance, reflecting that the target-mediated drug clearance declines more rapidly in children. In pediatric BCP-ALL, the median [interquartile range] cumulative area under the concentration–time curve was significantly higher among responders (n = 42) versus non-responders (n = 10) at the end of the first cycle (26.1 [18.9–35.0] vs 10.1 [9.19–16.1], × 103 ng*h/mL, p < 0.001). From simulations performed at the recommended pediatric phase II dose, inotuzumab ozogamicin exposure reached a similar level as observed in responding pediatric trial participants. Conclusions The pharmacokinetic profile of inotuzumab ozogamicin in pediatric patients with relapsed/refractory BCP-ALL was well described in this study. No dose adjustment is required clinically for pediatric patients with BCP-ALL based on the simulated inotuzumab ozogamicin exposure at the recommended pediatric phase II dose, promising efficacy and acceptable tolerability.
      PubDate: 2024-06-22
       
  • P2X3 Receptor Antagonist Eliapixant in Phase I Clinical Trials: Safety and
           Inter-ethnic Comparison of Pharmacokinetics in Healthy Chinese and
           Japanese Participants

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      Abstract: Background Afferent neuronal hypersensitization via P2X3 receptor signaling has been implicated as a driver of several disorders, including refractory chronic cough, endometriosis, diabetic neuropathic pain, and overactive bladder. Eliapixant, a selective P2X3 receptor antagonist, has been in clinical development for all four disorders. Objective This paper describes pharmacokinetic (PK) and safety data from two phase I studies of eliapixant in healthy Japanese and Chinese participants and compares those data within the two populations and with previous multiple dose data from Caucasian participants. Methods Two separate phase I, single-center, randomized, placebo-controlled studies were conducted with healthy male participants. The Japanese study was single-blind and the Chinese study was double-blind. Eliapixant was administered as an oral amorphous solid dispersion immediate-release tablet in strengths of 25 mg, 75 mg, and 150 mg. PK characteristics after a single dose (SD) and at steady state (multiple dose [MD], twice daily), adverse events (AEs), and tolerability were evaluated. A post hoc comparison of PK characteristics after SD of eliapixant in Japanese and Chinese participants, and after MD of eliapixant in Japanese, Chinese, and Caucasian participants, was performed. Results Overall, 36/39 participants enrolled in the Japanese/Chinese studies, respectively (mean [standard deviation] age 25.4 [6.5] and 26.7 [5.0] years, respectively). After SD administration, maximum plasma concentration (Cmax) was higher among Japanese than Chinese participants in the 25 mg and 75 mg dose groups, but comparable in the 150 mg dose group. The area under the concentration–time curve (AUC) was comparable between Japanese and Chinese participants in the 25 mg and 75 mg dose groups, but lower among Japanese participants in the 150 mg group. Half-lives after SD and MD administration were also comparable in Japanese and Chinese participants. The post hoc analysis included 26 Japanese, 30 Chinese, and 50 Caucasian participants. Comparable exposure (Cmax,md and AUC[0–12]md) was observed after MD administration of eliapixant in Chinese and/or Japanese compared with Caucasian participants (geometric mean inter-ethnic ratios close to 1). The trough plasma concentration after eliapixant 150 mg MD, which was assumed to be relevant to eliapixant efficacy, was comparable across all ethnicity groups. Most AEs reported in the Japanese (eliapixant 75 mg SD, n = 2; eliapixant 150 mg MD, n = 2) and Chinese participants (eliapixant 25 mg SD, n = 7; eliapixant 75 mg SD, n = 6; eliapixant 150 mg SD, n = 7; eliapixant 150 mg MD, n = 9; placebo SD, n = 5; placebo MD, n = 1) were of mild intensity. Higher incidences of AEs in the Chinese population were likely due to differing standards of AE reporting between investigators. Conclusion Eliapixant was well tolerated by Japanese and Chinese participants. The inter-ethnic evaluation demonstrated similar PK characteristics across Japanese, Chinese, and Caucasian participants. Registration ClinicalTrials.gov identifier numbers: NCT04265781 and NCT04802343.
      PubDate: 2024-06-21
       
  • Pharmacokinetics–Pharmacodynamics Modeling for Evaluating Drug–Drug
           Interactions in Polypharmacy: Development and Challenges

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      Abstract: Abstract Polypharmacy is commonly employed in clinical settings. The potential risks of drug–drug interactions (DDIs) can compromise efficacy and pose serious health hazards. Integrating pharmacokinetics (PK) and pharmacodynamics (PD) models into DDIs research provides a reliable method for evaluating and optimizing drug regimens. With advancements in our comprehension of both individual drug mechanisms and DDIs, conventional models have begun to evolve towards more detailed and precise directions, especially in terms of the simulation and analysis of physiological mechanisms. Selecting appropriate models is crucial for an accurate assessment of DDIs. This review details the theoretical frameworks and quantitative benchmarks of PK and PD modeling in DDI evaluation, highlighting the establishment of PK/PD modeling against a backdrop of complex DDIs and physiological conditions, and further showcases the potential of quantitative systems pharmacology (QSP) in this field. Furthermore, it explores the current advancements and challenges in DDI evaluation based on models, emphasizing the role of emerging in vitro detection systems, high-throughput screening technologies, and advanced computational resources in improving prediction accuracy.
      PubDate: 2024-06-18
       
  • Population Pharmacokinetics of Cabozantinib in Metastatic Renal Cell
           Carcinoma Patients: Towards Drug Expenses Saving Regimens

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      Abstract: Introduction Cabozantinib is one of the preferred treatment options in the latest metastatic renal cell carcinoma (mRCC) guidelines. Cabozantinib is also associated with high drug expenses irrespective of the used dose, because a flat-prizing model has been implemented. In addition, concomitant intake with a high-fat meal increases its bioavailability on average by 57%. Combined with the long terminal half-life of cabozantinib (99 h), this creates possibilities to extend the dosing interval to reduce drug expenses whilst maintaining equivalent exposure. Objectives The primary objective was to evaluate the population pharmacokinetic (POPPK) model of cabozantinib developed for its registration using real-world patients’ therapeutic drug monitoring (TDM) data. The secondary objective was to design, simulate, and evaluate alternative dose regimens with the aim to reduce drug expenses whilst maintaining comparable exposure. Methods Retrospective TDM data from mRCC patients treated with cabozantinib were obtained. The data were evaluated using the published Food and Drug Administration (FDA) cabozantinib POPPK model, a two-compartment disposition model with a dual (fast and slow) lagged first-order absorption process derived from FDA registration documents, as a basis. Subsequently, simulations of alternative drug expenses saving regimens were evaluated. Results Twenty-seven mRCC patients with 75 pharmacokinetic observations were included. Patients were treated for a median of 75 days with a median dose of 40 mg. Model evaluation results showed that the cabozantinib TDM concentrations were adequately predicted by the published FDA cabozantinib POPPK model, except for a slightly higher clearance (CL) of 3.11 L/h compared to the reported value (2.23 L/h). The simulation study indicated that an alternative dose regimen that consists of taking 60 mg of cabozantinib for 2 days and then skipping 1 day results in comparable average exposure when compared with a 40 mg daily dose, both without food interaction, while saving 33.3% of the total drug expenses per month. The food effect of a high-fat meal was also taken into account when simulating other alternative dose regimens; 40 mg every 72 h combined with a high-fat meal resulted in comparable exposure when compared with a 20 mg daily dose fasted, while saving 66.7% in drug expenses. Conclusions In this study, the optimized cabozantinib POPPK model resulted in adequate prediction of real-world cabozantinib pharmacokinetic data. Alternative dosing regimens with and without using known food interactions were proposed that resulted in potential strategies to significantly reduce cabozantinib drug expenses.
      PubDate: 2024-06-14
       
  • Utilising Endogenous Biomarkers in Drug Development to Streamline the
           Assessment of Drug–Drug Interactions Mediated by Renal Transporters: A
           Pharmaceutical Industry Perspective

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      Abstract: Abstract The renal secretion of many drugs is facilitated by membrane transporters, including organic cation transporter 2, multidrug and toxin extrusion protein 1/2-K and organic anion transporters 1 and 3. Inhibition of these transporters can reduce renal excretion of drugs and thereby pose a safety risk. Assessing the risk of inhibition of these membrane transporters by investigational drugs remains a key focus in the evaluation of drug–drug interactions (DDIs). Current methods to predict DDI risk are based on generating in vitro data followed by a clinical assessment using a recommended exogenous probe substrate for the individual drug transporter. More recently, monitoring plasma-based and urine-based endogenous biomarkers to predict transporter-mediated DDIs in early phase I studies represents a promising approach to facilitate, improve and potentially avoid conventional clinical DDI studies. This perspective reviews the evidence for use of these endogenous biomarkers in the assessment of renal transporter-mediated DDI, evaluates how endogenous biomarkers may help to expand the DDI assessment toolkit and offers some potential knowledge gaps. A conceptual framework for assessment that may complement the current paradigm of predicting the potential for renal transporter-mediated DDIs is outlined.
      PubDate: 2024-06-13
       
  • Dose-Response Study of Norepinephrine Infusion for Maternal Hypotension in
           Preeclamptic Patients Undergoing Cesarean Delivery Under Spinal Anesthesia
           

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      Abstract: Background and Objective Spinal anesthesia remains the preferred mode of anesthesia for preeclamptic patients during cesarean delivery. We investigated the incidence of maternal hypotension under spinal anesthesia during cesarean delivery, by comparing different prophylactic infusion rates of norepinephrine with normal saline. Methods We randomly allocated 180 preeclamptic patients (45 in each groups) aged 18–45 scheduled for cesarean delivery to receive one of four prophylactic norepinephrine infusions at doses of 0 (normal saline group), 0.025 (0.025 group), 0.05 (0.05 group), or 0.075 (0.075 group) µg/kg/min following spinal anesthesia. The primary endpoint was the incidence of maternal hypotension (systolic blood pressure < 80% of baseline). Results The incidence of maternal hypotension was reduced with different prophylactic infusion rates of norepinephrine (26.7%, 15.6%, and 6.7%) compared with normal saline (37.8%) with a significant decreasing trend (p = 0.002). As the infusion doses of norepinephrine increased, there is a significant decreasing trend in deviation of systolic blood pressure control (median performance error; median absolute performance error) from baseline (p < 0.001; p < 0.001) and need for rescue norepinephrine boluses (p = 0.020). The effective dose 50 and effective dose 90 of prophylactic norepinephrine infusion were − 0.018 (95% confidence interval − 0.074, 0.002) µg/kg/min and 0.065 (95% confidence interval 0.048, 0.108) µg/kg/min, respectively. Conclusions Prophylactic infusion of norepinephrine, as compared to no preventive measures, can effectively reduce the incidence of maternal hypotension in preeclamptic patients under spinal anesthesia during cesarean delivery, without increasing other adverse events for either the mother or neonate. Registration: Clinical trials.gov identifier number NCT04556370.
      PubDate: 2024-06-13
       
  • Pharmacogenetic Testing or Therapeutic Drug Monitoring: A Quantitative
           Framework

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      Abstract: Background Pharmacogenetic profiling and therapeutic drug monitoring (TDM) have both been proposed to manage inter-individual variability (IIV) in drug exposure. However, determining the most effective approach for estimating exposure for a particular drug remains a challenge. This study aimed to quantitatively assess the circumstances in which pharmacogenetic profiling may outperform TDM in estimating drug exposure, under three sources of variability (IIV, inter-occasion variability [IOV], and residual unexplained variability [RUV]). Methods Pharmacokinetic models were selected from the literature corresponding to drugs for which pharmacogenetic profiling and TDM are both clinically considered approaches for dose individualization. The models were used to simulate relevant drug exposures (trough concentration or area under the curve [AUC]) under varying degrees of IIV, IOV, and RUV. Results Six drug cases were selected from the literature. Model-based simulations demonstrated that the percentage of patients for whom pharmacogenetic exposure prediction is superior to TDM differs for each drug case: tacrolimus (11.0%), tamoxifen (12.7%), efavirenz (49.2%), vincristine (49.6%), risperidone (48.1%), and 5-fluorouracil (5-FU) (100%). Generally, in the presence of higher unexplained IIV in combination with lower RUV and IOV, exposure was best estimated by TDM, whereas, under lower unexplained IIV in combination with higher IOV or RUV, pharmacogenetic profiling was preferred. Conclusions For the drugs with relatively low RUV and IOV (e.g., tamoxifen and tacrolimus), TDM estimated true exposure the best. Conversely, for drugs with similar or lower unexplained IIV (e.g., efavirenz or 5-FU, respectively) combined with relatively high RUV, pharmacogenetic profiling provided the most accurate estimate for most patients. However, genotype prevalence and the relative influence of genotypes on the PK, as well as the ability of TDM to accurately estimate AUC with a limited number of samples, had an impact. The results could be used to support clinical decision making when considering other factors, such as the probability for severe side effects.
      PubDate: 2024-06-06
       
  • Development of a Physiologically Based Pharmacokinetic Population Model
           for Diabetic Patients and its Application to Understand
           Disease-drug–drug Interactions

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      Abstract: Introduction The activity changes of cytochrome P450 (CYP450) enzymes, along with the complicated medication scenarios in diabetes mellitus (DM) patients, result in the unanticipated pharmacokinetics (PK), pharmacodynamics (PD), and drug–drug interactions (DDIs). Physiologically based pharmacokinetic (PBPK) modeling has been a useful tool for assessing the influence of disease status on CYP enzymes and the resulting DDIs. This work aims to develop a novel diabetic PBPK population model to facilitate the prediction of PK and DDI in DM patients. Methods First, mathematical functions were constructed to describe the demographic and non-CYP physiological characteristics specific to DM, which were then incorporated into the PBPK model to quantify the net changes in CYP enzyme activities by comparing the PK of CYP probe drugs in DM versus non-DM subjects. Results The results show that the enzyme activity is reduced by 32.3% for CYP3A4/5, 39.1% for CYP2C19, and 27% for CYP2B6, while CYP2C9 activity is enhanced by 38% under DM condition. Finally, the diabetic PBPK model was developed through integrating the DM-specific CYP activities and other parameters and was further used to perform PK simulations under 12 drug combination scenarios, among which 3 combinations were predicted to result in significant PK changes in DM, which may cause DDI risks in DM patients. Conclusions The PBPK modeling applied herein provides a quantitative tool to assess the impact of disease factors on relevant enzyme pathways and potential disease-drug–drug-interactions (DDDIs), which may be useful for dosing regimen optimization and minimizing the DDI risks associated with the treatment of DM. Graphical
      PubDate: 2024-05-31
       
  • Application of Physiologically Based Pharmacokinetic Modeling to
           Characterize the Effects of Age and Obesity on the Disposition of
           Levetiracetam in the Pediatric Population

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      Abstract: Background Levetiracetam is an antiseizure medication used for several seizure types in adults and children aged 1 month and older; however, due to a lack of data, pharmacokinetic (PK) variability of levetiracetam is not adequately characterized in certain populations, particularly neonates, children younger than 2 years of age, and children older than 2 years of age with obesity. Objective This study aimed to address the gap by leveraging PK data from two prospective standard-of-care pediatric trials (n = 88) covering an age range from 1 month to 19 years, including those with obesity (64%), and applying a physiologically based PK (PBPK) modeling framework. Methods A published PBPK model of levetiracetam for children aged 2 years and older was extended to pediatric patients younger than 2 years of age and patients older than 2 years of age with obesity by accounting for the obesity and age-related changes in PK using PK-Sim® software. The prospective pediatric data, along with the literature data for neonates and children younger than 2 years of age, were used to evaluate the extended PBPK models. Results Overall, 82.4% of data fell within the 90% interval of model-predicted concentrations, with an average fold error within twofold of the accepted criteria. PBPK modeling revealed that children with obesity had lower weight-normalized clearances (0.053 L/h/kg) on average than children without obesity (0.063 L/h/kg). The effect of maturation was well-characterized, resulting in comparable PBPK-simulated, weight-normalized clearances for neonates and children younger than 2 years of age reported from the literature. Conclusions PBPK modeling simulations revealed that the current US FDA-labeled pediatric dosing regimen listed in the prescribing information can produce the required exposure of levetiracetam in these target populations with dose adjustments for children with obesity aged 4 years to younger than 16 years.
      PubDate: 2024-05-30
       
  • Comment on: “CYP3A4*22 Genotype‑Guided Dosing of Kinase Inhibitors in
           Cancer Patients”

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      PubDate: 2024-05-11
       
 
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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 1 - 200 of 253 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 29)
AAPS Open     Open Access   (Followers: 5)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
AboutOpen     Open Access  
ACS Pharmacology & Translational Science     Hybrid Journal   (Followers: 3)
Acta Pharmaceutica     Open Access   (Followers: 4)
Acta Pharmaceutica Indonesia     Open Access  
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Pharmacologica Sinica     Hybrid Journal   (Followers: 2)
Acta Physiologica Hungarica     Full-text available via subscription  
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 4)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 95)
Advanced Therapeutics     Hybrid Journal   (Followers: 1)
Advances in Medical, Pharmaceutical and Dental Research     Open Access   (Followers: 14)
Advances in Pharmacological and Pharmaceutical Sciences     Open Access   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15)
Advances in Pharmacology and Pharmacy     Open Access   (Followers: 7)
Advances in Traditional Medicine     Hybrid Journal   (Followers: 5)
Adverse Drug Reaction Bulletin     Full-text available via subscription   (Followers: 4)
AJP : The Australian Journal of Pharmacy     Full-text available via subscription   (Followers: 11)
Al-Azhar Journal of Pharmaceutical Sciences     Open Access   (Followers: 6)
Alternatives to Laboratory Animals     Full-text available via subscription   (Followers: 6)
American Journal of Cardiovascular Drugs     Hybrid Journal   (Followers: 20)
American Journal of Drug Discovery and Development     Open Access   (Followers: 3)
American Journal of Health-System Pharmacy     Full-text available via subscription   (Followers: 51)
American Journal of Pharmacology and Toxicology     Open Access   (Followers: 21)
American Journal of Therapeutics     Hybrid Journal   (Followers: 11)
Analytical Methods     Hybrid Journal   (Followers: 7)
Annales Pharmaceutiques Francaises     Full-text available via subscription   (Followers: 1)
Annals of Pharmacotherapy     Hybrid Journal   (Followers: 52)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 27)
Anti-Infective Agents     Hybrid Journal   (Followers: 5)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 6)
Antibiotics     Open Access   (Followers: 12)
Antibody Therapeutics     Open Access  
Antiviral Chemistry and Chemotherapy     Open Access   (Followers: 1)
Antiviral Research     Hybrid Journal   (Followers: 7)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Pharmacal Research     Full-text available via subscription   (Followers: 1)
Archives of Pharmacy and Pharmaceutical Sciences     Open Access   (Followers: 2)
Archives of Razi Institute     Open Access   (Followers: 1)
Archivos Venezolanos de Farmacología y Terapéutica     Open Access  
Ars Pharmaceutica     Open Access  
Asian Journal of Medical and Pharmaceutical Researches     Open Access  
Asian Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
Asian Journal of Research in Medical and Pharmaceutical Sciences     Open Access  
ASSAY and Drug Development Technologies     Hybrid Journal   (Followers: 4)
Australian Journal of Herbal Medicine     Full-text available via subscription   (Followers: 4)
Australian Pharmacist     Full-text available via subscription   (Followers: 7)
Autonomic & Autacoid Pharmacology     Hybrid Journal  
Avicenna Journal of Phytomedicine     Open Access   (Followers: 1)
Bangladesh Journal of Pharmacology     Open Access  
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11)
Behavioural Pharmacology     Hybrid Journal   (Followers: 2)
Biochemical Pharmacology     Hybrid Journal   (Followers: 9)
BioDrugs     Full-text available via subscription   (Followers: 4)
Biomaterials     Hybrid Journal   (Followers: 54)
Biomedical and Environmental Sciences     Full-text available via subscription   (Followers: 1)
Biomedicine & Pharmacotherapy     Full-text available via subscription   (Followers: 2)
Biometrical Journal     Hybrid Journal   (Followers: 6)
Biopharm International     Full-text available via subscription   (Followers: 8)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 12)
BMC Pharmacology     Open Access   (Followers: 3)
BMC Pharmacology & Toxicology     Open Access   (Followers: 5)
British Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 25)
British Journal of Pharmacology     Hybrid Journal   (Followers: 14)
British Journal of Pharmacy (BJPharm)     Open Access   (Followers: 2)
Bulletin of Faculty of Pharmacy, Cairo University     Open Access   (Followers: 2)
CADTH Technology Overviews     Free  
Canadian Journal of Pain     Open Access   (Followers: 3)
Canadian Journal of Physiology and Pharmacology     Hybrid Journal   (Followers: 1)
Canadian Pharmacists Journal / Revue des Pharmaciens du Canada     Hybrid Journal   (Followers: 3)
Cancer Biotherapy & Radiopharmaceuticals     Hybrid Journal  
Cancer Chemotherapy and Pharmacology     Hybrid Journal   (Followers: 4)
Cardiovascular Drugs and Therapy     Hybrid Journal   (Followers: 12)
Cardiovascular Therapeutics     Open Access   (Followers: 3)
Cephalalgia Reports     Open Access  
Chemical Research in Toxicology     Hybrid Journal   (Followers: 20)
ChemMedChem     Hybrid Journal   (Followers: 9)
Chinese Herbal Medicines     Full-text available via subscription   (Followers: 1)
Chinese Journal of Pharmaceutical Analysis     Full-text available via subscription  
Clinical and Experimental Pharmacology and Physiology     Hybrid Journal   (Followers: 3)
Clinical and Translational Science     Open Access   (Followers: 4)
Clinical Complementary Medicine and Pharmacology     Open Access   (Followers: 1)
Clinical Drug Investigation     Full-text available via subscription   (Followers: 6)
Clinical Medicine Insights : Therapeutics     Open Access  
Clinical Neuropharmacology     Hybrid Journal   (Followers: 2)
Clinical Pharmacist     Partially Free   (Followers: 11)
Clinical Pharmacokinetics     Full-text available via subscription   (Followers: 16)
Clinical Pharmacology & Therapeutics     Hybrid Journal   (Followers: 31)
Clinical Pharmacology in Drug Development     Hybrid Journal   (Followers: 2)
Clinical Pharmacology: Advances and Applications     Open Access   (Followers: 5)
Clinical Research and Regulatory Affairs     Hybrid Journal   (Followers: 5)
Clinical Therapeutics     Hybrid Journal   (Followers: 10)
Clinical Toxicology     Hybrid Journal   (Followers: 17)
Clinical Trials     Hybrid Journal   (Followers: 12)
CNS Drug Reviews     Open Access   (Followers: 3)
CNS Drugs     Full-text available via subscription   (Followers: 10)
Combination Products in Therapy     Open Access  
Consultant Pharmacist     Full-text available via subscription   (Followers: 2)
Consumer Drugs     Full-text available via subscription  
Contract Pharma     Full-text available via subscription  
Cosmetics     Open Access   (Followers: 4)
CPT : Pharmacometrics & Systems Pharmacology     Open Access   (Followers: 6)
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 16)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 22)
Current Bioactive Compounds     Hybrid Journal  
Current Cancer Therapy Reviews     Hybrid Journal   (Followers: 5)
Current Clinical Pharmacology     Hybrid Journal   (Followers: 3)
Current Drug Delivery     Hybrid Journal   (Followers: 6)
Current Drug Discovery Technologies     Hybrid Journal   (Followers: 5)
Current Drug Metabolism     Hybrid Journal   (Followers: 3)
Current Drug Safety     Hybrid Journal   (Followers: 8)
Current Drug Targets     Hybrid Journal   (Followers: 2)
Current Drug Therapy     Hybrid Journal   (Followers: 2)
Current Enzyme Inhibition     Hybrid Journal   (Followers: 2)
Current Issues in Pharmacy and Medical Sciences     Open Access   (Followers: 2)
Current Medical Science     Hybrid Journal  
Current Medicinal Chemistry     Hybrid Journal   (Followers: 7)
Current Molecular Pharmacology     Hybrid Journal  
Current Nanoscience     Hybrid Journal  
Current Neuropharmacology     Hybrid Journal   (Followers: 1)
Current Opinion in Pharmacology     Hybrid Journal   (Followers: 8)
Current Pharmaceutical Analysis     Hybrid Journal   (Followers: 1)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 8)
Current Pharmaceutical Design     Hybrid Journal   (Followers: 4)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Current Pharmacology Reports     Hybrid Journal  
Current Protocols in Pharmacology     Hybrid Journal  
Current Radiopharmaceuticals     Hybrid Journal   (Followers: 1)
Current Research in Drug Discovery     Open Access   (Followers: 1)
Current Research in Pharmacology and Drug Discovery     Open Access   (Followers: 6)
Current Therapeutic Research     Open Access   (Followers: 5)
Current trends in Biotechnology and Pharmacy     Open Access   (Followers: 7)
Current Vascular Pharmacology     Hybrid Journal   (Followers: 1)
Dhaka University Journal of Pharmaceutical Sciences     Open Access  
Die Pharmazie - An International Journal of Pharmaceutical Sciences     Full-text available via subscription   (Followers: 3)
Dose-Response     Open Access  
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 12)
Drug and Therapeutics Bulletin     Hybrid Journal   (Followers: 8)
Drug Delivery     Open Access   (Followers: 7)
Drug Delivery and Translational Research     Hybrid Journal   (Followers: 2)
Drug Design, Development and Therapy     Open Access   (Followers: 1)
Drug Development and Industrial Pharmacy     Hybrid Journal   (Followers: 25)
Drug Development Research     Hybrid Journal   (Followers: 8)
Drug Discovery Today     Full-text available via subscription   (Followers: 63)
Drug Metabolism and Disposition     Hybrid Journal   (Followers: 9)
Drug Metabolism and Pharmacokinetics     Hybrid Journal   (Followers: 4)
Drug Metabolism Letters     Hybrid Journal   (Followers: 2)
Drug Metabolism Reviews     Hybrid Journal   (Followers: 3)
Drug Research     Hybrid Journal   (Followers: 1)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
Drug Safety     Full-text available via subscription   (Followers: 81)
Drug Safety - Case Reports     Open Access   (Followers: 2)
Drug Target Insights     Open Access  
Drug, Healthcare and Patient Safety     Open Access   (Followers: 8)
Drugs     Full-text available via subscription   (Followers: 146)
Drugs & Aging     Full-text available via subscription   (Followers: 9)
Drugs & Therapy Perspectives     Full-text available via subscription   (Followers: 9)
Drugs : Real World Outcomes     Hybrid Journal   (Followers: 1)
Drugs in R & D     Full-text available via subscription   (Followers: 2)
Drugs of the Future     Full-text available via subscription   (Followers: 4)
East and Central African Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
EJNMMI Radiopharmacy and Chemistry     Open Access  
EMC - Cosmetologia Medica e Medicina degli Inestetismi Cutanei     Full-text available via subscription  
Emerging Trends in Drugs, Addictions, and Health     Open Access   (Followers: 2)
Environmental Toxicology and Pharmacology     Hybrid Journal   (Followers: 7)
Epilepsy Research     Hybrid Journal   (Followers: 8)
Ethiopian Pharmaceutical Journal     Full-text available via subscription   (Followers: 1)
EUREKA : Health Sciences     Open Access  
European Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 11)
European Journal of Drug Metabolism and Pharmacokinetics     Hybrid Journal   (Followers: 5)
European Journal of Hospital Pharmacy : Science and Practice (EJHP)     Hybrid Journal   (Followers: 5)
European Journal of Medicinal Plants     Open Access   (Followers: 2)
European Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 84)
European Journal of Pharmaceutics and Biopharmaceutics     Hybrid Journal   (Followers: 23)
European Journal of Pharmacology     Hybrid Journal   (Followers: 3)
European Medical, Health and Pharmaceutical Journal     Open Access   (Followers: 2)
European Neuropsychopharmacology     Hybrid Journal   (Followers: 8)
European Pharmaceutical Journal     Open Access  
European Review for Medical and Pharmacological Sciences     Full-text available via subscription   (Followers: 1)
Experimental and Clinical Psychopharmacology     Full-text available via subscription   (Followers: 7)
Expert Opinion on Drug Delivery     Hybrid Journal   (Followers: 18)
Expert Opinion on Drug Discovery     Hybrid Journal   (Followers: 16)
Expert Opinion on Emerging Drugs     Hybrid Journal   (Followers: 7)
Expert Opinion on Investigational Drugs     Hybrid Journal   (Followers: 10)
Expert Opinion on Orphan Drugs     Hybrid Journal  
Expert Opinion on Pharmacotherapy     Hybrid Journal   (Followers: 7)
Expert Review of Anti-infective Therapy     Full-text available via subscription   (Followers: 5)
Expert Review of Cardiovascular Therapy     Full-text available via subscription   (Followers: 4)
Expert Review of Clinical Pharmacology     Hybrid Journal   (Followers: 2)
Expert Review of Molecular Diagnostics     Full-text available via subscription   (Followers: 5)
Expert Review of Pharmacoeconomics & Outcomes Research     Full-text available via subscription   (Followers: 6)
Expert Review of Precision Medicine and Drug Development     Hybrid Journal   (Followers: 4)
Exploratory Research in Clinical and Social Pharmacy     Open Access   (Followers: 4)
Fitoterapia     Hybrid Journal   (Followers: 5)
Food Additives & Contaminants Part A     Hybrid Journal   (Followers: 8)
Frontiers in Drug Design & Discovery     Hybrid Journal   (Followers: 7)
Frontiers in Medical Technology     Open Access  

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