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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 401 - 253 of 253 Journals sorted alphabetically
Microbial Drug Resistance     Hybrid Journal   (Followers: 3)
Molecular Informatics     Hybrid Journal   (Followers: 5)
Molecular Pharmacology     Hybrid Journal   (Followers: 2)
Molekul     Open Access   (Followers: 1)
Natural Product Communications     Open Access  
Nature Reviews Drug Discovery     Full-text available via subscription   (Followers: 316)
Naunyn-Schmiedeberg's Archives of Pharmacology     Hybrid Journal  
NeuroMolecular Medicine     Hybrid Journal  
Neuropharmacology     Hybrid Journal   (Followers: 6)
Neuropsychopharmacology     Hybrid Journal   (Followers: 18)
Neuropsychopharmacology Reports     Open Access  
Nigerian Journal of Natural Products and Medicine     Full-text available via subscription  
OA Drug Design & Delivery     Open Access  
OA Medical Hypothesis     Open Access  
Obesity Facts     Open Access   (Followers: 8)
Open Pharmacoeconomics & Health Economics Journal     Open Access  
Open Pharmacology Journal     Open Access  
OpenNano     Open Access   (Followers: 1)
Orbital - The Electronic Journal of Chemistry     Open Access   (Followers: 1)
Oriental Pharmacy and Experimental Medicine     Partially Free   (Followers: 2)
Pain and Therapy     Open Access   (Followers: 3)
Particulate Science and Technology: An International Journal     Hybrid Journal   (Followers: 1)
PDA Journal of Pharmaceutical Science and Technology     Full-text available via subscription   (Followers: 36)
Pediatric Drugs     Full-text available via subscription   (Followers: 4)
Pediatric Pharmacology     Open Access   (Followers: 1)
Pharmaceutica Analytica Acta     Open Access  
Pharmaceutical Biology     Open Access  
Pharmaceutical Care-La Farmacoterapia     Open Access  
Pharmaceutical Chemistry Journal     Hybrid Journal  
Pharmaceutical Development and Technology     Hybrid Journal   (Followers: 21)
Pharmaceutical Executive     Full-text available via subscription   (Followers: 6)
Pharmaceutical Fronts     Open Access   (Followers: 6)
Pharmaceutical Historian     Open Access  
Pharmaceutical Journal     Free   (Followers: 8)
Pharmaceutical Journal of Sri Lanka     Open Access  
Pharmaceutical Medicine     Full-text available via subscription   (Followers: 4)
Pharmaceutical Nanotechnology     Hybrid Journal  
Pharmaceutical Patent Analyst     Full-text available via subscription   (Followers: 3)
Pharmaceutical Research     Hybrid Journal   (Followers: 97)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 16)
Pharmaceutical Technology     Full-text available via subscription   (Followers: 6)
Pharmaceuticals     Open Access   (Followers: 4)
Pharmacia     Open Access  
PharmacoEconomics     Full-text available via subscription   (Followers: 26)
PharmacoEconomics & Outcomes News     Full-text available via subscription   (Followers: 4)
PharmacoEconomics German Research Articles     Full-text available via subscription  
PharmacoEconomics Spanish Research Articles     Hybrid Journal   (Followers: 1)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 34)
Pharmacogenetics and Genomics     Hybrid Journal   (Followers: 1)
Pharmacogenomics     Hybrid Journal   (Followers: 7)
Pharmacogenomics and Personalized Medicine     Open Access   (Followers: 2)
Pharmacogenomics Journal     Hybrid Journal   (Followers: 5)
Pharmacognosy Communications     Partially Free  
Pharmacognosy Magazine     Open Access   (Followers: 2)
Pharmacognosy Research     Open Access   (Followers: 2)
Pharmacological Reports     Hybrid Journal  
Pharmacological Research     Hybrid Journal   (Followers: 1)
Pharmacological Research - Modern Chinese Medicine     Open Access  
Pharmacological Reviews     Hybrid Journal   (Followers: 2)
Pharmacology     Full-text available via subscription  
Pharmacology & Therapeutics     Hybrid Journal   (Followers: 3)
Pharmacology & Pharmacy     Open Access   (Followers: 1)
Pharmacology Biochemistry and Behavior     Hybrid Journal   (Followers: 2)
Pharmacology Research & Perspectives     Open Access  
Pharmacon : Jurnal Farmasi Indonesia     Open Access  
Pharmacopsychiatry     Hybrid Journal   (Followers: 3)
Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy     Hybrid Journal   (Followers: 38)
Pharmactuel     Open Access   (Followers: 1)
Pharmacy     Open Access   (Followers: 4)
Pharmacy & Pharmacology     Open Access  
Pharmacy Education     Full-text available via subscription   (Followers: 11)
Pharmacy Practice (Internet)     Open Access   (Followers: 8)
Pharmakon : Arzneimittel in Wissenschaft und Praxis     Full-text available via subscription   (Followers: 1)
PharmaNutrition     Hybrid Journal   (Followers: 3)
PharmaTutor     Open Access  
Pharmazeutische Industrie     Full-text available via subscription   (Followers: 11)
Pharmazeutische Zeitung     Full-text available via subscription   (Followers: 15)
Pharmazie in Unserer Zeit (Pharmuz)     Hybrid Journal   (Followers: 18)
Physiology International     Full-text available via subscription   (Followers: 3)
Plant Products Research Journal     Full-text available via subscription  
Planta Medica     Hybrid Journal   (Followers: 4)
Planta Medica International Open     Open Access  
Prescriber     Hybrid Journal   (Followers: 9)
Progress in Neuro-Psychopharmacology and Biological Psychiatry     Hybrid Journal   (Followers: 8)
Psychiatry and Clinical Psychopharmacology     Open Access   (Followers: 1)
Psychopharmacology     Hybrid Journal   (Followers: 16)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
PZ Prisma : Materialien zur Fort- und Weiterbildung     Full-text available via subscription  
Redox Report     Open Access  
Regulatory Mechanisms in Biosystems     Open Access   (Followers: 1)
Regulatory Toxicology and Pharmacology     Hybrid Journal   (Followers: 41)
Research & Reviews : A Journal of Drug Design & Discovery     Full-text available via subscription  
Research & Reviews : A Journal of Pharmaceutical Science     Full-text available via subscription  
Research & Reviews : A Journal of Pharmacognosy     Full-text available via subscription  
Research & Reviews : A Journal of Pharmacology     Full-text available via subscription   (Followers: 1)
Research in Pharmaceutical Sciences     Open Access   (Followers: 3)
Research in Social and Administrative Pharmacy     Hybrid Journal   (Followers: 3)
Research Journal of Pharmacognosy     Open Access  
Research Results in Pharmacology     Open Access  
Reviews of Physiology, Biochemistry and Pharmacology     Hybrid Journal   (Followers: 4)
Reviews on Clinical Pharmacology and Drug Therapy     Full-text available via subscription  
Revista Colombiana de Ciencias Químico-Farmacéuticas     Open Access  
Revista Cubana de Plantas Medicinales     Open Access   (Followers: 1)
Revista de Ciências Farmacêuticas Básica e Aplicada     Open Access  
Revista Mexicana de Ciencias Farmaceuticas     Open Access  
Revue de Médecine et de Pharmacie     Full-text available via subscription  
Safety and Risk of Pharmacotherapy     Open Access   (Followers: 1)
Saudi Pharmaceutical Journal     Open Access  
Scandinavian Journal of Clinical and Laboratory Investigation     Hybrid Journal   (Followers: 8)
Scientia Pharmaceutica     Open Access  
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Seminars in Oncology Nursing     Full-text available via subscription   (Followers: 10)
Separation Science plus (SSC plus)     Hybrid Journal  
Side Effects of Drugs Annual     Full-text available via subscription   (Followers: 2)
Skin Pharmacology and Physiology     Full-text available via subscription   (Followers: 6)
Substance Abuse : Research and Treatment     Open Access   (Followers: 5)
Suchttherapie     Hybrid Journal   (Followers: 1)
Sustainable Chemistry and Pharmacy     Full-text available via subscription   (Followers: 1)
Synfacts     Hybrid Journal   (Followers: 5)
SynOpen     Open Access  
The Botulinum J.     Hybrid Journal  
The Brown University Psychopharmacology Update     Hybrid Journal   (Followers: 2)
The Medical Letter     Full-text available via subscription   (Followers: 18)
The Pink Sheet     Full-text available via subscription   (Followers: 12)
The Pink Sheet Daily     Full-text available via subscription   (Followers: 5)
Therapeutic Advances in Drug Safety     Open Access   (Followers: 3)
Therapeutic Advances in Psychopharmacology     Open Access   (Followers: 4)
Therapeutic Advances in Vaccines     Hybrid Journal   (Followers: 1)
Therapeutic Drug Monitoring     Hybrid Journal   (Followers: 5)
Therapeutic Innovation & Regulatory Science     Hybrid Journal   (Followers: 7)
Thérapie     Full-text available via subscription   (Followers: 1)
TheScientist     Free   (Followers: 6)
Toxicological & Environmental Chemistry     Hybrid Journal   (Followers: 2)
Toxicological Research     Hybrid Journal  
Toxicological Sciences     Hybrid Journal   (Followers: 11)
Toxicology     Hybrid Journal   (Followers: 19)
Toxicology and Applied Pharmacology     Hybrid Journal   (Followers: 25)
Toxicology and Industrial Health     Hybrid Journal   (Followers: 6)
Toxicology in Vitro     Hybrid Journal   (Followers: 12)
Toxicology International     Full-text available via subscription   (Followers: 5)
Toxicology Letters     Hybrid Journal   (Followers: 16)
Toxicology Mechanisms and Methods     Hybrid Journal   (Followers: 9)
Toxicology Research     Partially Free   (Followers: 8)
Toxicon     Hybrid Journal   (Followers: 5)
Toxicon : X     Open Access  
Toxin Reviews     Hybrid Journal  
Translational Psychiatry     Open Access   (Followers: 14)
Trends in Peptide and Protein Sciences     Open Access  
Trends in Pharmacological Sciences     Full-text available via subscription   (Followers: 21)
Tropical Journal of Pharmaceutical Research     Open Access  
Ukrainian Biopharmaceutical Journal     Open Access  
Vascular Pharmacology     Hybrid Journal   (Followers: 2)
World Mycotoxin Journal     Hybrid Journal   (Followers: 3)
Yakugaku Zasshi     Open Access   (Followers: 1)
Zeitschrift für Phytotherapie     Hybrid Journal   (Followers: 1)
Актуальні питання фармацевтичної та медичної науки та практики     Open Access  
Фармацевтичний часопис     Open Access  

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Similar Journals
Journal Cover
Therapeutic Drug Monitoring
Journal Prestige (SJR): 0.656
Citation Impact (citeScore): 2
Number of Followers: 5  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0163-4356 - ISSN (Online) 1536-3694
Published by LWW Wolters Kluwer Homepage  [297 journals]
  • Meropenem to Treat Valproic Acid Intoxication

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      Authors: Smolders; Elise J.; Ter Heine, Rob; Natsch, Stephanie; Kramers, Kees
      Abstract: imageAbstract: This therapeutic drug monitoring (TDM) grand round describes a patient with serious valproic acid intoxication. A total valproic acid level of 844 mg/L and an unbound valproic acid level of 604 mg/L were observed. Meropenem was administered to enhance the clearance of valproic acid. This off-label usage of meropenem is based on the drug–drug interaction between carbapenems and valproic acid, which reduced the level of valproic acid within 24 hours after administration.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • What Is the Therapeutic Reference Range for Levetiracetam' Grand
           Round/A Case Study

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      Authors: Couderc; Sylvain; Chouchane, Mondher; Saint-Marcoux, Franck
      Abstract: Abstract: The Therapeutic Drug Monitoring guidelines of Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie had proposed a therapeutic reference range of 10–40 mg/L for levetiracetam in 2011. In the first version of the 2017 update, it was changed to 20–40 mg/L; however, 5 months later, in an erratum version, it was changed back to 10–40 mg/L. In this study, the authors agree with the range to 10–40 mg/L but discuss to what extent a wider interval may be proposed for certain patients.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • A Patient With Sepsis-Induced Multiorgan Failure and Increasing Serum
           Methadone Concentration: A Case Study

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      Authors: Dale; Gro Helen; Holmaas, Gunhild; Berg, Jon A.; Riedel, Bettina; Schjøtt, Jan; Bjånes, Tormod K.
      Abstract: imageAbstract: The authors describe a patient with substance use disorder admitted to the hospital with septic shock and multiorgan failure, in whom the serum concentration of methadone kept increasing despite discontinuation of the drug. Therapeutic drug monitoring was performed to monitor the methadone serum concentration during treatment of the underlying diseases.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • High Tacrolimus Intrapatient Variability and Subtherapeutic
           Immunosuppression are Associated With Adverse Kidney Transplant Outcomes

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      Authors: Mendoza Rojas; Aleixandra; Hesselink, Dennis A.; van Besouw, Nicole M.; Dieterich, Marjolein; de Kuiper, Ronella; Baan, Carla C.; van Gelder, Teun
      Abstract: imageBackground: Kidney transplant recipients with high intrapatient variability (IPV) in tacrolimus (Tac) exposure experience more rejection and reduced graft survival. To understand the underlying pathophysiology of this association, the authors investigated whether patients with high tacrolimus IPV have a more activated immune system than patients with low IPV. In addition, exposure to tacrolimus and mycophenolic acid (MPA) was studied in relation to rejection and graft survival.Methods: At the time of patient inclusion (5–7 years post-transplantation), the frequency of donor-reactive cells was determined by enzyme-linked immunosorbent assay, and the development of donor-specific anti-Human Leukocyte Antigen antibodies (DSA) was measured by Luminex Single Antigen assay. Tacrolimus IPV was retrospectively calculated between 6 and 12 months and the exposure to tacrolimus and MPA was determined between 1 and 5 years post-transplantation.Results: A total of 371 kidney transplant recipients were included in this study, of whom 56 developed a rejection episode after 12 months and 60 experienced graft failure after 5–7 years. No correlations were found between tacrolimus IPV or immunosuppression exposure and the number of donor-reactive cells after 5 years of transplantation. DSA were detected more often in patients with low exposure to both tacrolimus and MMF [4/21 (19%) versus 17/350 (4.9%), P = 0.04]. In this cohort, neither tacrolimus IPV nor low overall immunosuppression exposure was associated with a higher incidence of rejection. However, regression analysis showed that a higher tacrolimus IPV was associated with an increased incidence of graft failure (odds ratio = 1.03, P = 0.02).Conclusions: This study verifies the relationship between high tacrolimus IPV and impaired kidney allograft survival in long-term follow-up. DSA was also found to be more prevalent in patients with subtherapeutic concentrations of tacrolimus and MPA. An increased prevalence of donor-specific alloreactivity is yet to be demonstrated in patients with high IPV.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Drug–Drug Interactions With Cyclosporine in the Anti-Hepatitis C Viral
           PrOD Combination Regimen of Paritaprevir/Ritonavir–Ombitasvir and
           Dasabuvir in Organ Transplant Recipients With Severe Hepatic Fibrosis or
           Cirrhosis

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      Authors: Huang; Ying-Yu; Huang, Yu-Hsuan; Wu, Tsai-Hung; Loong, Che-Chuan; Hsu, Chia-Chen; Chou, Yueh-Ching; Chang, Yuh-Lih
      Abstract: imageBackground: The clinical guidelines suggest that the dosing of cyclosporine (CsA), during combination therapy with paritaprevir/ritonavir–ombitasvir and dasabuvir (PrOD), would be only one-fifth of the pre-PrOD total daily dose to be administered once daily. However, this dosing may not be applicable to all patients depending on their clinical condition. This study focuses on the pharmacokinetic dynamics of PrOD with CsA in Asian organ transplant recipients with severe liver fibrosis or cirrhosis who undergo concurrent treatment with PrOD treatment and CsA. The efficacy and safety of PrOD treatment was also evaluated.Methods: Data from 7 patients obtained between January 2017 and September 2017 were retrospectively analyzed. Determinations of the blood concentrations of CsA were made, whether used as a single treatment or in combination therapy with PrOD.Results: The combination regimen compared with CsA administered alone resulted in a 4.53-fold and 5.52-fold increase in the area under the concentration–time curve from time 0–12 hours (AUC0–12 h) of CsA on days 1 and 15, respectively. In addition, the maximal concentration, time to maximum concentration, and terminal phase elimination half-life (t1/2) of CsA were increased during the combined treatment of PrOD and CsA. The authors proposed reducing the CsA dosage during PrOD treatment to one-seventh of that of the pre-PrOD treatment of the total daily dose to maintain target CsA levels. All patients achieved sustained virologic responses at week 12. There were no episodes of serious adverse events or graft rejections observed.Conclusions Although the combination with PrOD significantly affects the pharmacokinetics of CsA, it is effective and safe with regular monitoring of the CsA blood concentrations and appropriate CsA dose adjustment.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Drug–Drug Interactions Between Mycophenolic Acid and Proton Pump
           Inhibitors: A Systematic Review and Meta-Analysis

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      Authors: Sakuludomkan; Wannachai; Na Takuathung, Mingkwan; Dukaew, Nahathai; Koonrungsesomboon, Nut
      Abstract: imagePurpose: The objective of the present study was to determine the impact of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA).Methods: PubMed, Embase, Web of Sciences, and Scopus were systematically searched to identify relevant studies reporting pharmacokinetic parameters [including trough concentration (C0), maximum concentration (Cmax), time to maximum concentration (Tmax), the dose-adjusted area under the concentration–time curve from time 0–12 hours (AUC0–12 h/D), and half-life (t1/2)], and pharmacodynamic outcomes of MPA (eg, acute graft rejection and adverse drug reactions), with and without PPI administration. Pooled effect estimates were calculated using a random-effects model.Results: Twelve studies involving 473 participants were eligible for inclusion, 11 of which were included in the meta-analysis. PPI exposure was significantly associated with lower C0 [mean difference (MD) = −0.62 mg/L; P = 0.003] lower Cmax (MD = −4.71 mg/L; P = 0.01), and longer Tmax (MD = 0.30 hours; P = 0.0001) of MPA. However, no significant association was observed between PPI exposure and AUC0–12 h/D, t1/2, or any pharmacodynamic outcomes. Based on subgroup analysis, it can be suggested that a significant association between PPI exposure and altered MPA pharmacokinetics was mainly associated with mycophenolate mofetil but not enteric-coated mycophenolate sodium.Conclusions: Coadministration of PPIs and mycophenolate mofetil significantly altered the pharmacokinetics of MPA, particularly by decreasing MPA absorption. However, PPI-MPA interactions did not impact pharmacodynamic outcomes of MPA.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Inosine Triphosphate Pyrophosphatase and NUDT15 are Good Predictors of
           Clinical Outcomes in Thiopurine-Treated Chinese Patients with Inflammatory
           Bowel Disease

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      Authors: Luo; Xuemei; Yan, Simin; Jin, Lu; Zhu, Huaijun; Zhang, Xiaoqi; Ge, Weihong
      Abstract: imageBackground: Although the relationship between NUDT15 and thiopurine-induced leukopenia has been proven in previous studies, no prominent factors explaining interindividual variations in its active metabolite, 6-thioguanine nucleotide (6-TGN), and clinical efficacy have been identified. In this study, the correlation between genotypes (thiopurine S-methyltransferase, NUDT15, and ITPA polymorphisms), 6-TGN concentrations, and clinical outcomes (efficacy and side effects) in patients with inflammatory bowel disease were investigated.Methods: In total, 160 patients with inflammatory bowel disease were included, and the 3 genotyped genes and 6-TGN levels were measured by high-performance liquid chromatography. Statistical analyses and calculations were performed to determine their relationships.Results: ITPA genotypes and 6-TGN concentration were both associated with the clinical effectiveness of azathioprine (P = 0.036 and P = 4.6 × 10−7), with a significant correlation also detected between them (P = 0.042). Patients with ITPA variant alleles exhibited higher 6-TGN levels than those with the wild-type allele. In addition, the relationship between NUDT15 and leukopenia and neutropenia was confirmed (P = 1.79 × 10−7 and 0.002).Conclusions: In summary, it is recommended that both ITPA and NUDT15 genotyping should be performed before azathioprine initiation. Moreover, the 6-TGN concentration should be routinely monitored during the later period of treatment.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Optimal Sampling Strategy and Threshold of Serum Vancomycin Concentration
           in Elderly Japanese Patients Undergoing High-Flux Hemodialysis

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      Authors: Ogawa; Akio; Hira, Daiki; Tsujimoto, Masayuki; Nishiguchi, Kohshi; Endo, Masanori; Ono, Toshiaki; Hatta, Tsuguru; Terada, Tomohiro; Morita, Shin-ya
      Abstract: imageBackground: The optimal sampling points and thresholds for initial serum vancomycin (VCM) concentrations have not been determined in hemodialysis (HD) patients. To clarify this, multiple blood tests were performed, and the correlations between VCM concentrations at several sampling points and the area under the concentration–time curve for 24 hours (AUC24h) were analyzed.Methods: A single-center, prospective observational study was conducted. Patients with end-stage renal failure who received VCM treatment while undergoing chronic maintenance HD were enrolled in this study. HD was performed using a high-flux membrane as the dialyzer. After VCM administration, 7 points were sampled between the first and second HD. The AUC24h after the end of the first HD (AUC0–24) and that before the end of the second HD (AUC24–48) were calculated using the linear trapezoidal method. Correlation analysis and simple regression analysis between AUC24h and serum concentrations were performed at each sampling point.Results: Nine patients were evaluated. Strong correlations were found between AUC24–48 and serum concentrations at 24 hours after the initiation of VCM treatment following the first HD (C24h, R = 0.983 and P < 0.001), between AUC0–24 and C24h (R = 0.967 and P < 0.001), and between AUC24–48 and serum concentration just before the second HD (Cpre(HD2), R = 0.965 and P < 0.001). Regression equations with high coefficients of determination (R2> 0.9) were obtained, and a C24h of ≥18.0 mg/L and a Cpre(HD2) of ≥16.5 mg/L were required to achieve an AUC24–48 value of ≥400 mg·h/L. In addition, a C24h of ≤23.3 mg/L was estimated to satisfy the AUC0–24 range of ≤600 mg·h/L.Conclusions: C24h and Cpre(HD2) are optimal sampling points for predicting VCM-AUC24h in HD patients.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Optimal Teicoplanin Dosing Regimen in Neonates and Children Developed by
           Leveraging Real-World Clinical Information

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      Authors: Yamada; Takaaki; Emoto, Chie; Fukuda, Tsuyoshi; Motomura, Yoshitomo; Inoue, Hirosuke; Ohga, Shouichi; Ieiri, Ichiro
      Abstract: imageBackground: Teicoplanin is a glycopeptide antibiotic used for the treatment of methicillin-resistant Staphylococcus aureus infections. To ensure successful target attainment, therapeutic drug monitoring–informed dosage adjustment is recommended. However, it relies on the experience of the clinician and the frequency of drug measurements. This study aimed to design a new optimal dosing regimen of teicoplanin with a maintenance dosing strategy for neonates and children based on their physiological characteristics.Methods: Data from teicoplanin-treated patients (n = 214) were collected from electronic medical records. Covariate analyses were performed using population pharmacokinetic (PK) modeling with 399 serum teicoplanin concentrations from 48 neonates and 166 children. Multiple PK simulations were conducted to explore optimal dosing regimens that would allow control of the trough concentration to the target of 15–30 mg/L quicker than the current standard regimen.Results: Allometrically scaled body weight, postmenstrual age (PMA), renal function, and serum albumin were implemented as substantial covariates for teicoplanin clearance in a two-compartment PK model. Covariate analyses and comprehensive simulation assessments recommended the following modifications to the current regimen: (1) decreased dose for premature babies (PMA ≤28 weeks), (2) decreased dose for children with renal dysfunction, and (3) increased dose for children (0.5–11 years) with an estimated glomerular filtration rate of ≥90 mL/min/1.73 m2.Conclusions: This study leverages real-world clinical information and proposes new optimal dosing regimens for teicoplanin in neonates and children through PK modeling and simulation analyses, taking into account the age, including PMA, and renal function of patients.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Decreased Systemic Busulfan Exposure After Oral Dosing With Concomitant
           Levetiracetam Compared With Phenytoin

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      Authors: Artul; Tareq; Henig, Israel; Nassar, Laila; Yehudai-Ofir, Dana; Scherb, Inna; Lurie, Yael; Efrati, Edna; Zuckerman, Tsila; Kurnik, Daniel
      Abstract: imageBackground: Busulfan (Bu) conditioning used in hematopoietic stem cell transplantation may induce seizures, and prophylactic antiepileptic treatment is recommended. Following updated guidelines, in August 2019, the adult hematopoietic stem cell transplantation department of the Rambam Health Care Campus (Haifa, Israel) switched the antiepileptic prophylaxis protocol from phenytoin to oral levetiracetam during oral Bu conditioning. The aim of this study was to compare the pharmacokinetic parameters of Bu after oral dosing between patients receiving phenytoin and those receiving levetiracetam prophylaxis.Methods: This study was a retrospective cohort study in adults undergoing myoablative conditioning with oral Bu between August 2018 and August 2020. Bu pharmacokinetic parameters (AUC0-6, C0, Cmax, and Tmax) were compared in patients treated with phenytoin comedication (during the year before the change in policy) and levetiracetam comedication (during the year after the change). Potential confounders were accounted for including age, azole comedication, and body weight.Results: There were no significant differences in demographic and clinical parameters or weight-corrected Bu dose between the phenytoin group (n = 28) and the levetiracetam group (n = 25). There was no difference in the rate of voriconazole comedication, but fluconazole was more common in the phenytoin group (P = 0.026). The median AUC0-6 was significantly lower in the levetiracetam group (949 μM*min; IQR = 806 to 1101 μM*min) than in the phenytoin group (1208 μM*min; IQR = 1087 to 1389 μM*min; P < 0.001). This is a clinically significant difference of 258 μM*min (21%). Azole use was not associated with Bu exposure.Conclusions: The findings suggest that, after treatment with oral Bu, oral levetiracetam comedication is associated with reduced systemic exposure compared with phenytoin comedication, possibly because of decreased bioavailability.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Development of a Sensitive and High-Throughput Assay for Simultaneous
           Quantification of 5 Tyrosine Kinase Inhibitors and 2 Active Metabolites in
           Human Plasma Using Ultra-high Performance Liquid Chromatography Coupled to
           Tandem Mass Spectrometry

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      Authors: Sumimoto; Takahiro; Nakahara, Ryosuke; Suzuki, Yosuke; Tanaka, Ryota; Yoshida, Natsumi; Ogata, Masao; Itoh, Hiroki
      Abstract: imageBackground: Breakpoint cluster region-Abelson (BCR-ABL) tyrosine kinase inhibitors (TKIs) demonstrate improved therapeutic efficacy in chronic myeloid leukemia (CML). However, drug–drug interactions, nonadherence, and host-related factors may influence plasma concentrations. Therefore, therapeutic drug monitoring may be necessary for patients presenting inadequate treatment responses or adverse events. Herein, the authors aimed to develop a more sensitive and high-throughput method than those previously reported to simultaneously quantify 5 TKIs (imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) and 2 active metabolites (N-desmethyl imatinib and N-desmethyl ponatinib) using ultra-performance liquid chromatography coupled with tandem mass spectrometry.Methods: Plasma samples were prepared according to a solid-phase extraction protocol using an Oasis MCX µElution plate. The assay fulfilled the requirements of the US Food and Drug Administration for assay validation, with a lower limit of quantification of 0.2 ng/mL for dasatinib, 0.3 ng/mL for N-desmethyl ponatinib, 0.5 ng/mL for N-desmethyl imatinib, bosutinib, and ponatinib, and 2.5 ng/mL for imatinib and nilotinib.Results: Within-batch and batch-to-batch precision at the lower limit of quantification and quality control levels were within 14.3% and 10.9%, respectively. Within-batch and batch-to-batch accuracies ranged from 15.5% to 13.0% and 5.70% to 7.03%, respectively. A positive electrospray ionization mode was used with a run time of 6.0 minutes. The assay applicability was verified by the successful measurement of 78 clinical samples from patients undergoing CML therapy.Conclusions: The method allows assessment of trough concentrations of TKIs and active metabolites in patients with CML, and hence can be used to assess blood samples in routine clinical settings.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Validation and Clinical Application of a Liquid
           Chromatography–Ultraviolet Detection Method to Quantify Dolutegravir in
           Dried Blood Spots

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      Authors: Akinloye; Abdulafeez; Eniayewu, Oluwasegun; Adeagbo, Babatunde; Bolaji, Oluseye; Olagunju, Adeniyi
      Abstract: imageBackground: Dolutegravir is currently the preferred component of first-line antiretroviral therapy. To facilitate clinical pharmacology studies in key populations, quantitative analytical methods compatible with microsampling and adaptable to resource-limited settings are desirable. The authors developed and validated a liquid chromatography–ultraviolet detection method to quantify dolutegravir in dried blood spots (DBS).Methods: Calibration standards and quality control samples were prepared by spotting 50 μL of dolutegravir-spiked whole blood on each circle of DBS cards. Three spots (two 6-mm punches/spot) were extracted with methanol. Chromatographic separation was achieved with gradient elution of acetonitrile/potassium phosphate monobasic buffer (pH 5) on a reverse-phase C18 column (flow rate, 1 mL/min) using pioglitazone as the internal standard. UV detection was performed at 260 nm. In the clinical pharmacokinetic study, DBS from finger prick was collected from participants (n = 10) at 8 time points over 12 hours postdosing, with paired plasma at 1 and 12 hours. The method was used to quantify dolutegravir, estimating pharmacokinetic parameters. Agreement between DBS and plasma concentrations was evaluated using linearity and Bland–Altman plots.Results: The method was validated over the concentration range of 0.4–10 mcg/mL, accuracy was 102.4%–114.8%, and precision was 3.4%–14.7%. The mean recovery was 42.3% (%CV: 8.3). The mean (±SD) dolutegravir concentration in DBS was 37.5% (±3.8%) lower than that in the plasma. DBS-derived and measured plasma concentrations showed strong correlation with linearity (R2 = 0.9804) and Bland–Altman plots. Means (%CV) of area under curve, Cmax, and C24 from the DBS-derived plasma concentration were 37.8 (23.2) mcg·h/mL, 2.7 (24.7) mcg/mL, and 1.34 (31.6) mcg/mL, respectively.Conclusions: The application of this simple, accurate, and precise method will expand opportunities for clinical assessment of dolutegravir in resource-limited settings.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Longitudinal Monitoring of Hair Cortisol Using Liquid
           Chromatography–Mass Spectrometry to Prevent Hypercortisolism in Patients
           Undergoing Glucocorticoid Replacement Therapy

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      Authors: Kostolanská; Katarína; Šiprová, Helena; Bartečků, Elis; Juřica, Jan; Řiháček, Ivan; Táborská, Eva; Souček, Miroslav; Peš, Ondřej
      Abstract: imageObjective: Currently available methods for endogenous cortisol monitoring in patients with hormonal insufficiency rely on measurements of plasma levels only at a single time point; thus, any kind of chronic exposure to cortisol is challenging to evaluate because it requires collecting samples at different time points. Hair cortisol levels acquired longitudinally better reflected chronic exposure (both cortisol synthesis and deposition) and may significantly contribute to better outcomes in glucocorticoid replacement therapies.Design: Twenty-two patients on cortisol substitution therapy were monitored for plasma, urinary, and hair cortisol levels for 18 months to determine whether hair cortisol may serve as a monitoring option for therapy setting and adjustment.Methods: Plasma and urinary cortisol levels were measured using standardized immunoassay methods, and segmented (∼1 cm) hair cortisol levels were monitored by liquid chromatography coupled to mass spectrometry. A log-normal model of the changes over time was proposed, and Bayesian statistics were used to compare plasma, urinary, and hair cortisol levels over 18 months.Results and conclusions: Hair cortisol levels decreased over time in patients undergoing substitutional therapy. The residual variance of hair cortisol in comparison to plasma or urinary cortisol levels was much lower. Thus, longitudinal monitoring of hair cortisol levels could prove beneficial as a noninvasive tool to reduce the risk of overdosing and improve the overall patient health.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Interindividual Variability in the Bioavailability of Gabapentin Enacarbil
           Extended Release in Healthy Adults: An Analysis of Data From 6 Phase I
           Studies

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      Authors: Lal; Ritu; Ellenbogen, Aaron; Gidal, Barry
      Abstract: imageBackground: The absorption and bioavailability of oral gabapentin are associated with a high degree of interindividual variability. Gabapentin enacarbil, a prodrug of gabapentin, is well absorbed and provides sustained, dose-proportional exposure to gabapentin. The aim of this analysis was to describe the interindividual variability in the bioavailability of gabapentin after gabapentin enacarbil administration in healthy subjects.Methods: Gabapentin pharmacokinetic (PK) parameters after an oral dose of gabapentin enacarbil 1200 mg (2 600-mg tablets) were compared across 6 phase I studies in healthy adults (n = 12 per study). The distribution of bioavailability values was assessed in all studies.Results: The mean PK parameters of gabapentin were consistent across the trials: maximum concentration range: 6.4–7.9 μg/mL, time to maximum concentration range: 5.2–8.2 hours, area under the plasma–concentration curve extrapolated from time 0 to infinity or at steady state range: 70.8–109.4 μg·h/mL, and bioavailability range: 64.8%–82.9%. Overall, the mean bioavailability was 74.1% (SD, 14.1; coefficient of variation, 19.1%). Individual bioavailability across all studies ranged from 42% to 100%.Conclusions: Gabapentin PK after gabapentin enacarbil administration was consistent across studies, with low interindividual variability in bioavailability. Gabapentin enacarbil may provide more consistent and predictable exposure to gabapentin than oral gabapentin formulations.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Impact of ABCB1 Polymorphisms on Lacosamide Serum Concentrations in Uygur
           Pediatric Patients With Epilepsy in China

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      Authors: Zhao; Ting; Li, Hong-jian; Feng, Jie; Zhang, Hui-lan; Ting-ting, Wang; Ma, Long; Yu, Jing; Zhao, Wen-bo; Sun, Li; Yu, Lu-hai; Sun, Yan
      Abstract: imageBackground: P-glycoprotein, encoded by ABCB1 (or MDR1), may contribute to drug resistance in epilepsy by limiting gastrointestinal absorption and brain access to antiseizure medications. The study aimed to evaluate the impact of ABCB1 polymorphisms on lacosamide (LCM) serum concentrations in Uygur pediatric patients with epilepsy.Methods: The serum concentrations of LCM were determined by ultrahigh performance liquid chromatography, and the ABCB1 polymorphism was analyzed through polymerase chain reaction–fluorescence staining in situ hybridization. The χ2 test and the Fisher exact test were used to analyze the allelic and genotypic distributions of ABCB1 polymorphisms between the drug-resistant and drug-responsive patient groups. Differences in steady-state and dose-corrected LCM serum concentrations between different genotypes were analyzed using the one-way analysis of variance and the Mann–Whitney test.Results: A total of 131 Uygur children with epilepsy were analyzed, and of them, 41 demonstrated drug resistance. The frequency of the GT genotype of ABCB1 G2677T/A was significantly higher in the drug-resistant group than that in the drug-responsive group (P < 0.05, OR = 1.966, 95% CI, 1.060–3.647). Patients with the G2677T/A-AT genotype had a statistically significantly lower concentration-to-dose (CD) value than patients with the G2677T/A-GG genotype (mean: 0.6 ± 0.2 versus 0.8 ± 0.5 mcg/mL per mg/kg, P < 0.001). Significantly lower LCM serum concentrations were observed in ABCB1 C3435T CT and TT genotype carriers than those in the CC carriers (P = 0.008 and P = 0.002), and a significantly lower LCM CD value was observed in ABCB1 C3435T CT genotype carriers than that in the CC carriers (P = 0.042).Conclusions: ABCB1 G2677T/A and C3435T polymorphisms may affect LCM serum concentrations and treatment efficacy in Uygur pediatric patients with epilepsy, leading to drug resistance in pediatric patients.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
  • Development of a Novel Analytical Method for Determining Trazodone in
           Human Plasma by Liquid Chromatography Coupled With Mass Spectrometry
           Coupled With Automatic 2-Dimensional Liquid Chromatograph-Mass
           Spectrometer Coupler 9500 and Its Application to Therapeutic Drug
           Monitoring

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      Authors: Ding; Jing; Zhang, Yan; Cui, Xiaohua; Zhao, Caiping; Zhang, Suo
      Abstract: imageBackground: Trazodone (TZD) is a tetracyclic serotonin antagonist and reuptake inhibitor that is used as a second-generation phenylpiperazine antidepressant. However, the plasma concentrations of TZD have shown individual variations in clinical practice. Quantification of TZD plasma concentrations may be an effective and valuable method to balance the clinical efficacy and adverse reactions. This study aimed to establish a novel liquid chromatography coupled with mass spectrometry (LC-MS) assay for measuring TZD concentrations in human plasma for therapeutic drug monitoring (TDM).Methods: After protein precipitation with acetonitrile, LC-MS quantification of TZD was performed in the multiple reaction monitoring mode with chromatographic separation using a mobile phase of MeOH and 0.1% formic acid in water. This method validation intends to investigate specificity, sensitivity, linearity, precision, accuracy, recovery, matrix effect, and stability according to United states food and drug administration guidelines.Results: This method showed good selectivity because no interfering peaks were observed in the plasma samples during the 2-minute run time. The range of the calibration curve was 1–3000 ng/mL. The detection and quantification limits were 0.3 and 1 ng/mL, respectively. The intraday and interday accuracies were 96.5%–103.4%, with precision relative SD% values of
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT-
       
 
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