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- Synergizing pharmacometrics and pharmacovigilance for medication error
management: the case of secukinumab-
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Abstract: Purpose To demonstrate the effective integration of pharmacometrics and pharmacovigilance in managing medication errors, highlighted by a case involving secukinumab in a patient with hidradenitis suppurativa. Methods We present the case of a 41-year-old male with progressive hidradenitis suppurativa, unresponsive to multiple antibiotic regimens and infliximab treatment. Due to a medication error, the patient received 300 mg of secukinumab daily for 4 days instead of weekly, totaling 1200 mg. The regional pharmacovigilance center assessed potential toxicity, and a pharmacometric analysis using a population pharmacokinetic model was performed to inform dosing adjustments. Results Clinical data indicated that the received doses were within a non-toxic range. No adverse effects were observed. Pharmacometric simulations revealed a risk of underexposure due to the dosing error. Based on these simulations, it was recommended to restart monthly secukinumab injections on day 35 after the initial dose. Measured plasma concentrations before re-administration confirmed the model's accuracy. Conclusion This case highlights the crucial collaboration between clinical services, pharmacovigilance, and pharmacometrics in managing medication errors. Such interdisciplinary efforts ensure therapeutic efficacy and patient safety by maintaining appropriate drug exposure levels.
PubDate: 2024-09-01
- How can polymyxin B be dosed based on current pharmacokinetic
knowledge'-
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PubDate: 2024-09-01
- Development and validation of individualized tacrolimus dosing software
for Chinese pediatric liver transplantation patients: a population
pharmacokinetic approach-
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Abstract: Objective We aim to describe the population pharmacokinetics (PPK) of tacrolimus in Chinese pediatric patients under 4 years old after liver transplantation and to develop individualized tacrolimus dosing software. Methods A total of 663 blood concentrations from 85 patients aged 4.57 months to 3.97 years were collected in this study. PPK analysis was performed using a nonlinear mixed effects modeling approach with the software, Phoenix. Using C#, an individualized tacrolimus dosing software was created. The software was then used to predict the concentrations of another ten pediatric liver transplantation patients to verify the accuracy of said software. The predictive error (PE) and the absolute predictive error (APE) for each predicted time point were computed. Results A one-compartment model with first-order elimination best fitted the data. The apparent volume of distribution (V/F) and apparent clearance (CL/F) were 198.65 L and 2.41 L/h. Postoperative days (POD), total bilirubin (TBIL), and the use of voriconazole significantly influenced tacrolimus apparent clearance. The incorporation of an increasing number of actual blood drug concentrations into the prediction resulted in a decrease in both PE (72%, 17%, 7%) and APE (87%, 53%, 26%). Conclusions A qualified PPK model of tacrolimus was developed in Chinese pediatric patients. The individualized tacrolimus dosing software could be used as a suitable tool for the personalization of tacrolimus dosing for pediatric patients after liver transplantation.
PubDate: 2024-09-01
- Reliability and validity of the Swedish indicator ‘Drugs that should be
avoided in older people’—an appraisal of a set of potentially
inappropriate medications-
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Abstract: Purpose To analyse the reliability and validity of the Swedish indicator ‘Drugs that should be avoided in older people’. Methods From a previous study that included consecutive primary care patients ≥ 65 years of age, all patients ≥ 75 years of age were analysed. Two physicians independently screened their medication lists and medical records, applying the Swedish indicator which includes potentially inappropriate medications (PIMs): long-acting benzodiazepines, drugs with anticholinergic action, tramadol, propiomazine, codeine, and glibenclamide. The clinical relevance of identified PIMs was independently assessed. Thereafter, the physicians determined in consensus whether some medical action related to the drug treatment was medically justified and prioritised before the next regular visit. If so, the drug treatment was considered inadequate, and if not, adequate. Results A total of 1,146 drugs were assessed in 149 patients (75‒99 years, 62% female, 0‒20 drugs per patient). In 29 (19%) patients, at least one physician identified ≥ 1 PIM according to the indicator at issue; 24 (16%) patients were concordantly identified with ≥ 1 such PIM (kappa: 0.89). Of 26 PIMs concordantly identified, the physicians concordantly assessed four as clinically relevant and 12 as not clinically relevant (kappa: 0.17). After the consensus discussion, six (4%) patients had ≥ 1 PIM according to the studied indicator that merited action. Using the area under the receiver operating characteristic (ROC) curve, the indicator did not outperform chance in identifying inadequate drug treatment: 0.56 (95% confidence interval: 0.46 to 0.66). Conclusion The Swedish indicator has strong reliability regarding PIM detection but does not validly reflect the adequacy of drug treatment.
PubDate: 2024-09-01
- Apixaban plasma concentrations in patients with obesity
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Abstract: Purpose Routine therapeutic drug monitoring of apixaban is currently not recommended but may however be warranted in some situations and for some patient groups to provide better and safer treatment. Due to limited data on apixaban concentrations in different subpopulations, it is still unclear which group of patients could possibly gain from monitoring. The purpose of this study was to examine apixaban exposure in patients with obesity compared with normal-weight patients. Methods Forty patients with obesity (mean BMI 39.4 kg/m2) and 40 controls with normal weight (mean BMI 23.4 kg/m2), treated with apixaban 5 mg twice daily were included. The patients were matched for age, sex, and renal function. Trough and peak apixaban concentrations were measured with LC‒MS/MS methodology. Results The median trough concentrations in patients with obesity (58.7, range 10.7–200.7 ng/ml) were slightly higher than those in patients with normal weight (52.0, range 31.0–150.9 ng/ml) (p < 0.05). Notably, the variability in trough concentration was considerably higher in patients with obesity. Peak concentrations were similar in both groups, with a median of 124.5 ng/ml (range 82.0–277.5) and 113.5 ng/ml (range 75.5–334.6) in patients with obesity and normal weight, respectively. Conclusion Apixaban exposure did not vary substantially between obese and normal weight matched controls, implying that general dose adjustments are not required. However, vast interindividual variability was observed in patients with obesity, suggesting that measuring the concentrations could be valuable for specific patients. Further research is needed to identify which specific patients may benefit from this approach.
PubDate: 2024-09-01
- Quantitative evaluation of the efficacy and safety profiles of two types
of targeted inhibitors combined with endocrine therapy in
ER+/HER2− metastatic breast cancer-
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Abstract: Purpose The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2− metastatic breast cancer. Methods A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3–4 adverse events were summarized using the random-effects model of a single-arm meta-analysis. Results This study included 44 arms from 48 publications, with a total sample size of 7881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and an ORR of 40%, whereas PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and an ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events. Conclusion Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2− metastatic breast cancer in clinical guidelines.
PubDate: 2024-09-01
- Trends in statin use for the primary prevention of atherosclerotic
cardiovascular disease among US adults by demographic characteristics,
1999–2020-
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Abstract: Purpose Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality worldwide. Statins, which are effective in preventing ASCVD, are underused, particularly for primary prevention. This study examined trends in statin use for primary ASCVD prevention from 1999 to 2020, focusing on demographic variations. Methods Utilizing data from the National Health and Nutrition Examination Survey, the present study includes individuals aged 18 years and older who had a greater than 10% risk of ASCVD over 10 years, and excluded patients with existing ASCVD. Subgroup analyses by demographic categories were performed. We calculated the changes in statin usage and used linear and quadratic tests to assess the linear and nonlinear trends in those changes. Results A total of 10,037 participants were included. Statin usage increased from 16.16% in 1999 to 36.24% in 2010, and 41.74% in 2020 (quadratic P-value < 0.001). In the 18–44 years age group, statin usage increased from 2.52% in 1999 to 8.14% in 2020 (linear P-value = 0.322), showing no significant linear trend. In the “never-married” group, statin usage increased from 19.16% in 1999 to 30.05% in 2020 (linear P-value = 0.256). Conclusion Statin usage has shown a positive trend among populations requiring primary prevention for ASCVD. Currently, health policies are proving effective. However, the overall statin usage rate remains less than 50%. Additionally, young and never-married individuals should also receive special attention regarding statin usage as primary treatment for ASCVD.
PubDate: 2024-09-01
- Population pharmacokinetic, pharmacodynamic and efficacy modeling of SB12
(proposed eculizumab biosimilar) and reference eculizumab-
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Abstract: Purpose To describe, compare similarity of pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of SB12 and reference eculizumab (ECU) and find clinically significant covariate relationships. Methods The PK, PD (terminal complement activity) and efficacy (LDH) data of SB12 and ECU were obtained from 289 subjects from phase I and phase III studies. One- and two-compartment PK models with first-order elimination were evaluated for SB12 and ECU. For PD and efficacy, both direct and indirect models were tested. The impact of covariates on PK, PD and efficacy parameters was assessed. Relationship between PK/PD and PD/efficacy was characterized. This modeling was performed using NONMEM version 7.4 (Icon Development Solutions, Ellicott City, MD, USA). Results The two-compartment model adequately described the PK of SB12 and ECU, and the subject’s weight was chosen as a clinically significant covariate affecting drugs’ clearance and central volume of distribution. Treatment group was not a significant covariate affecting clearance. The direct response model using inhibitory sigmoid Emax and sigmoid Emax relationship well described the PK/PD relationship and PD/efficacy relationship of SB12 and ECU, respectively. Through this modeling, the relationships between PK, PD and efficacy were characterized. There were no differences in PK, PD and efficacy parameters between SB12 and ECU in pooled populations of healthy subjects and paroxysmal nocturnal haemoglobinuria (PNH) patients. Conclusion The population modeling showed PK, PD and efficacy similarities between SB12 and ECU in pooled population of healthy subjects and PNH patients, supporting the totality of evidence on biosimilarity for SB12.
PubDate: 2024-09-01
- Clinical and biochemical characteristics, and outcome in 33 patients with
ceftriaxone-induced liver injury-
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Abstract: Purpose To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. Methods Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. Results A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. Conclusion Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia.
PubDate: 2024-09-01
- Treatment-related adverse events in patients with advanced breast cancer
receiving adjuvant AKT inhibitors: a meta-analysis of randomized
controlled trials-
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Abstract: Introduction Incorporation of AKT inhibitors into adjuvant therapy for advanced or metastatic breast cancer has improved clinical outcomes. However, the safety of AKT inhibitors should be better evaluated, given the possibility of prolonging survival and impacting patient quality of life. Our aim was to assess how the addition of AKT inhibitors to adjuvant therapy affects treatment-related adverse events. Methods We evaluated binary outcomes with risk ratios (RRs), with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses. Results A total of seven RCTs comprising 1619 patients with BC. The adverse effects that show significance statistical favoring the occurrence of adverse effects in AKT inhibitor were diarrhea (RR 3.05; 95% CI 2.48–3.75; p < 0.00001; I2 = 49%), hyperglycemia (RR 3.4; 95% CI 1.69–6.83; p = 0.00058; I2 = 75%), nausea (RR 1.69; 95% CI 1.34–2.13; p = 0.000008; I2 = 42%), rash (RR 2.79; 95% CI 1.49–5.23; p = 0.0013; I2 = 82%), stomatitis (RR 2.24; 95% CI 1.69–2.97; p < 0.00001; I2 = 16%) and vomiting (RR 2.99; 95% CI 1.85–4.86; p = 0.00009; I2 = 42%). There was no significant difference between the groups for alopecia (p = 0.80), fatigue (p = 0.087), and neuropathy (p = 0.363380). Conclusion The addition of AKT inhibitors to adjuvant therapy was associated with an increase in treatment-related adverse events. These results provide safety information for further clinical trials evaluating AKT inhibitor therapy for patients with metastatic BC. Clinicians should closely monitor patients for treatment-related adverse events to avoid discontinuation of therapy and morbidity caused by these early-stage therapies. Graphical abstract 
PubDate: 2024-09-01
- Assessment of body mass-related covariates for rifampicin pharmacokinetics
in healthy Caucasian volunteers-
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Abstract: Purpose Currently, body weight-based dosing of rifampicin is recommended. But lately, fat-free mass (FFM) was reported to be superior to body weight (BW). The present evaluation aimed to assess the influence of body mass-related covariates on rifampicin’s pharmacokinetics (PK) parameters in more detail using non-linear mixed effects modeling (NLMEM). Methods Twenty-four healthy Caucasian volunteers were enrolled in a bioequivalence study, each receiving a test and a reference tablet of 600 mg of rifampicin separated by a wash-out period of at least 9 days. Monolix version 2023R1 was used for NLMEM. Monte Carlo simulations (MCS) were performed to visualize the relationship of body size descriptors to the exposure to rifampicin. Results A one-compartment model with nonlinear (Michaelis–Menten) elimination and zero-order absorption kinetics with a lag time best described the data. The covariate model including fat-free mass (FFM) on volume of distribution (V/F) and on maximum elimination rate (Vmax/F) lowered the objective function value (OFV) by 56.4. The second-best covariate model of sex on V/F and Vmax/F and BW on V/F reduced the OFV by 51.2. The decrease in unexplained inter-individual variability on Vmax/F in both covariate models was similar. For a given dose, MCS showed lower exposure to rifampicin with higher FFM and accordingly in males compared to females with the same BW and body height. Conclusion Our results indicate that beyond BW, body composition as reflected by FFM could also be relevant for optimized dosing of rifampicin. This assumption needs to be studied further in patients treated with rifampicin.
PubDate: 2024-09-01
- Characteristics and preventability of medication-related admissions for
acute kidney injury and dehydration in elderly patients-
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Abstract: Purpose Patients with impaired renal function using medication that affects glomerular filtration rate are at increased risk of developing acute kidney injury (AKI) leading to hospital admissions. The risk increases during periods of dehydration due to diarrhoea, vomiting or fever (so-called “sick days”), or high environmental temperatures (heat wave). This study aims to gain insight into the characteristics and preventability of medication-related admissions for AKI and dehydration in elderly patients. Methods Retrospective case series study in patients aged ≥ 65 years with admission for acute kidney injury, dehydration or electrolyte imbalance related to dehydration that was defined as medication-related. General practitioner’s (GP) patient records including medication history and hospital discharge letters were available. For each admission, patient and admission characteristics were collected to review the patient journey. A case-by-case assessment of preventability of hospital admissions was performed. Results In total, 75 admissions were included. Most prevalent comorbidities were hypertension, diabetes, and known impaired renal function. Diuretics and RAS-inhibitors were the most prevalent medication combination. Eighty percent of patients experienced non-acute onset of symptoms and 60% had contacted their GP within 2 weeks prior to admission. Around 40% (n = 29) of admissions were considered potentially preventable if pharmacotherapy had been timely and adequately adjusted. Conclusion A substantial proportion of patients admitted with AKI or dehydration experience non-acute onset of symptoms and had contacted their GP within 2 weeks prior to admission. Timely adjusting of medication in these patients could have potentially prevented a considerable number of admissions.
PubDate: 2024-09-01
- Population pharmacokinetics of free and liposome-encapsulated mitoxantrone
in patients with relapsed/refractory lymphoma or small cell lung cancer-
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Abstract: Objective This study is aimed at investigating the pharmacokinetic (PK) characteristics of pegylated liposomal mitoxantrone (PLM) in patients with relapsed/refractory lymphoma or small cell lung cancer (SCLC) by constructing population pharmacokinetic (popPK) models for both liposome-encapsulated mitoxantrone and free mitoxantrone. Methods A total of 23 patients with relapsed/refractory lymphoma and 42 patients with SCLC were included. A popPK model was simultaneously developed utilizing a non-linear mixed effects model (NONMEM) to explore the PK profiles of liposome-encapsulated mitoxantrone and free mitoxantrone. Clearance (CL) and distribution volume (V) were calculated, and covariate analysis was employed to evaluate the influence of patient disease type, demographic information, and biochemical indicators of liver and kidney function on PK parameters. Results The concentration-time profiles for both liposome-encapsulated mitoxantrone and free mitoxantrone were described by a one-compartment model. The release (Rel) of liposome-encapsulated mitoxantrone to free mitoxantrone was determined to be 0.0191 L/h, and the V of liposome-encapsulated mitoxantrone was 2.32 L. The apparent CL of free mitoxantrone was estimated at 1.66 L/h. The apparent V of free mitoxantrone was 35.8 L in patients with relapsed/refractory lymphoma and 22.2 L for patients with SCLC. In patients with relapsed/refractory lymphoma, lower maximum concentration (Cmax) and higher apparent V of free mitoxantrone were observed compared with patients with SCLC. Conclusion The popPK characteristics of both liposome-encapsulated and free mitoxantrone in patients with relapsed/refractory lymphoma or SCLC were effectively described by a one-compartment model.
PubDate: 2024-09-01
- The safety and efficacy of bevacizumab in treatment of recurrent low-grade
glioma: a systematic review and meta-analysis-
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Abstract: Background Central nervous system (CNS) tumors are among the most common malignancies in various age ranges. Low-grade glioma (LGG) can account for nearly 30% of pediatric CNS malignancies. Progression or recurrence after the first-line treatments is common among these patients. Therefore, more treatments are required. Bevacizumab as an anti-VEGF antibody has come into the spotlight recently and is especially used in relapse or recurrence settings. This review aims to study the safety and efficacy of bevacizumab for patients with recurrent LGG. Methods This study was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Scopus, Web of Science, and Embase were comprehensively searched using the relevant key terms until 24th August 2023 to retrieve the studies that investigated clinical outcomes of bevacizumab in patients with recurrent LGG. All statistical analysis was performed by STATA v.17. Results A total of 1306 papers were gathered, out of which 13 were incorporated in the meta-analysis. The pooled incidence rate of treatment according to the RANO scale was 70% (95% CI = 43–98%) for objective response rate, 26% (95% CI = 58–96%) for partial response, 21% (95% CI = 15–28%) for minor response, 14% (95% CI = 3–24%) for complete response, 48% (95% CI = 37–59%) for stable disease, and 8% (95% CI = 4–11%) for progressive disease. Furthermore, according to progressive survival after treatment, it was 4% (95% CI = −1 to 9%) for 6-month PFS, 41% (95% CI = 32–50%) for 2-year PFS, and 29% (95% CI = 22–35%) for 3-year PFS. Conclusion According to the RANO scale and PFS, clinicians should be aware that Bevacizumab could be a favorable alternative therapy for recurrent LGG. Furthermore, bevacizumab exhibits minimal toxicity and high tolerability in recurrent LGG.
PubDate: 2024-09-01
- Assessment of a systematic approach for implementing novel medications in
clinical practice: an observational study with dapagliflozin-
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Abstract: Objective To assess a systematic implementation approach for introducing dapagliflozin to individuals with heart failure and reduced ejection fraction in an outpatient clinical setting. Methods Retrospective medical record data were analysed. All individuals diagnosed with heart failure who resided within the hospital catchment area and had visited cardiology or internal medicine department between 2010 and 2019 were screened by using the main inclusion criteria from the DAPA-HF trial. The effectiveness of the previously described seven-step systematic implementation approach was assessed by the proportion receiving information letter, dapagliflozin treatment, follow-ups at 2–12 weeks and 12 months post-dapagliflozin initiation, persistence on dapagliflozin, adverse events, and reasons for discontinuation. Results Of the 2433 individuals, 352 met the main DAPA-HF trial criteria in step 2. After exclusions in steps 3 and 4, 191 individuals remained. Of these, 158 were invited for eligibility discussion in step 5, with 107 having received an information letter beforehand. In step 6, dapagliflozin was prescribed to 69 individuals, and in step 7, follow-ups were conducted with 56 individuals at 2–12 weeks and 62 individuals at 12 months. Sixty out of 69 persisted on dapagliflozin after 12 months. Adverse events were reported by nine individuals. Discontinuation was attributed to reasons such as urinary tract infections, genital or abdominal discomfort, and hypotension. Conclusion The systematic introduction of dapagliflozin to heart failure patients was effective. Despite this, challenges in uniformly implementing procedures across patients were evident, emphasizing the necessity for a systematic implementation approach.
PubDate: 2024-09-01
- Population pharmacokinetics and dosage optimization of linezolid in
Chinese older patients-
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Abstract: Purpose To assess the pharmacokinetics and pharmacodynamics of linezolid in a retrospective cohort of hospitalized Chinese older patients. Methods Patients > 60 years of age, who received intravenous linezolid (600 mg), were included. A population pharmacokinetics (PPK) model was established using nonlinear mixed-effects modeling. The predictive performance of the final model was assessed using goodness-of-fit plots, bootstrap analyses, and visual predictive checks. Monte Carlo simulations were used to evaluate the achievement of a pharmacodynamics target for the area under the serum concentration–time curve/minimum inhibitory concentration (AUC0–24/MIC). Results A total of 210 samples were collected from 120 patients. A one-compartment PPK model with linear elimination best predicted the linezolid plasma concentrations. Linezolid clearance (CL) was 4.22 L h−1 and volume of distribution (Vd) was 45.80 L; serum uric acid (SUA) was a significant covariate of CL. Conclusion The results of this study indicated that the standard dose was associated with a risk of overexposure in older patients, particularly those with high SUA values; these patients would benefit from a lower dose (300 mg every 12 h).
PubDate: 2024-09-01
- Reference guides for the safe use of drugs during pregnancy: a systematic
review and comparative analysis-
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Abstract: Purpose To comprehensively evaluate and compare all the available reference guides for the safe use of drugs during pregnancy, with the goal of determining the scientificity and reliability of these reference guides. Methods We searched PubMed, EMbase, CNKI, Wanfang Database, and VIP database to comprehensively identify the available reference guides. Moreover, we selected 103 drugs based on relevant literatures, and compared the recommendations of each drug from different reference guides. Results A total of 14 available reference guides were identified. However, none of these reference guides assessed the risk of bias of original studies or the quality of current evidence. Seven reference guides adopted expert consensus method to formulate pregnancy recommendations, while the rest reference guides did not report the formation method. Moreover, 77.7% of the selected drugs had inconsistent recommendations among different reference guides. In addition, the referenced human and animal studies for the same drug differed among different reference guides. Conclusion Our results indicate that current reference guides for the safe use of drugs during pregnancy are less scientific and reliable, and there are considerable discrepancies in recommendations from different reference guides concerning drug use during pregnancy. The reasons for the discrepancies in recommendations include ① the literature search in most reference guides was not comprehensive, ② none of the available reference guides assessed the risk of bias of original studies or the quality of current evidence, and ③ the method adopted by current reference guides to formulate recommendations had obvious subjectivity and lacked of scientificity.
PubDate: 2024-08-26
- Evaluation of pharmacokinetic target attainment and hematological toxicity
of linezolid in pediatric patients-
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Abstract: Background Linezolid is commonly used to treat severe and/or resistant Gram-positive infections. Few studies have assessed its pharmacokinetic (PK) target attainment in pediatrics. Objective To evaluate the percentage of pediatrics achieving the PK targets of linezolid with standard dosing regimens and to assess the incidence and risk factors associated with its hematologic toxicity. Methods This prospective observational study included pediatric patients aged 0–14 who received linezolid for suspected or proven Gram-positive infections. Linezolid trough concentrations and the 24-h area under the curve (AUC24) were estimated, and hematologic toxicity was assessed. Results Seventeen pediatric patients (5 neonates and 12 older pediatrics) were included. A wide variability was observed in linezolid’s trough and AUC24 (ranging from 0.5 to 14.4 mg/L and from 86 to 700 mg.h/L, respectively). The median AUC24 was significantly higher in neonates than older pediatrics (436 [350–574] vs. 200 [134–272] mg,h/L, P = 0.01). Out of all patients, only 41% achieved adequate drug exposure (AUC24 160–300 mg.h/L and trough 2–7 mg/L), with 24% having subtherapeutic, and 35% having higher-than-optimal exposures. Hematological toxicity was observed in 53% of cases. Identified risk factors include treatment duration over 7 days, baseline platelet counts below 150 × 109/L, sepsis/septic shock, and concomitant use of meropenem. Conclusions Linezolid’s standard dosing failed to achieve its PK targets in approximately half of our pediatric cohort. Our findings highlight the complex interplay between the risk factors of linezolid-associated hematological toxicity and underscore the importance of its vigilant use and monitoring, particularly in pediatrics with concomitant multiple risk factors.
PubDate: 2024-08-25
- Correction to: Use of antibiotics in the early COVID‑19 pandemic in
Poland, the Netherlands and Spain, from erraticism to (more) logic-
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PubDate: 2024-08-22
- Prognostic effect of a vasopressin V2 receptor antagonist in acute
congestive heart failure patients with hypoperfusion, the wet–cold
pattern-
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Abstract: Purpose This study investigated whether the oral vasopressin V2 receptor antagonist tolvaptan has beneficial effects on mortality in real-world congestive heart failure (CHF) patients with hypoperfusion (i.e. the wet–cold pattern), from the viewpoint of cardiorenal syndrome. Methods Data on 5511 consecutive CHF patients were extracted from the Tokyo CCU Network data registry. Congestion and hypoperfusion were defined by Nohria–Stevenson clinical profiles at the time of hospitalization. Propensity scores for tolvaptan use were calculated for each patient and used to assemble two matched cohorts of patients receiving tolvaptan or not in the CHF with and without hypoperfusion groups. Results Of the entire study cohort, 1073 patients (19%) had CHF with hypoperfusion (i.e. the wet–cold pattern). In-hospital mortality was significantly higher for CHF patients with than without hypoperfusion (log-rank, P < 0.001). The rate of tolvaptan use did not differ significantly between CHF patients with and without hypoperfusion (15% vs. 14%, respectively; P = 0.7848). In the propensity-matched CHF with hypoperfusion cohort, there was a significant association between the use of tolvaptan and a reduction in in-hospital mortality (log-rank, P = 0.0052). Conversely, in the matched CHF without hypoperfusion cohort, tolvaptan use was not associated with in-hospital mortality (log-rank, P = 0.4417). Conclusion There was a significant association between the use of tolvaptan and a reduction in in-hospital mortality in CHF patients with, but not without, hypoperfusion. These findings hint at possible individualized therapies for patients with CHF.
PubDate: 2024-08-21
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