Genetic algorithm guided population pharmacokinetic model development for simvastatin, concurrently or non-concurrently co-administered with amlodipine

2013 ◽  
Vol 54 (2) ◽  
pp. 141-149 ◽  
Author(s):  
Ayyappa Chaturvedula ◽  
Mark E. Sale ◽  
Howard Lee
Keyword(s):  
Genetic Algorithm ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Model Development ◽  
Population Pharmacokinetic

scholarly journals Population Pharmacokinetics of Tenofovir in HIV-1-Uninfected Members of Serodiscordant Couples and Effect of Dose Reporting Methods

2016 ◽  
Vol 60 (9) ◽  
pp. 5379-5386 ◽  
Author(s):  
Yanhui Lu ◽  
Vineet Goti ◽  
Ayyappa Chaturvedula ◽  
Jessica E. Haberer ◽  
Michael J. Fossler ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Drug Concentration ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Electronic Monitoring ◽  
Model Development ◽  
Population Pharmacokinetic ◽  
Main Trial ◽  
Patient Reported ◽  
Hiv 1

ABSTRACTAntiretroviral preexposure prophylaxis (PrEP) with once-daily dosing of tenofovir and tenofovir-emtricitabine was shown to be effective for preventing HIV-1 infection in individuals who had HIV-1-seropositive partners (the Partners PrEP Study). We developed a population pharmacokinetic model for tenofovir and investigated the impacts of different dose reporting methods. Dosing information was collected as patient-reported dosing information (PRDI) from 404 subjects (corresponding to 1,280 drug concentration records) from the main trial and electronic monitoring-based adherence data collected from 211 subjects (corresponding to 327 drug concentration records) in an ancillary adherence study. Model development was conducted with NONMEM (7.2), using PRDI with a steady-state assumption or using PRDI replaced with electronic monitoring records where available. A two-compartment model with first-order absorption was the best model in both modeling approaches, with the need for an absorption lag time when electronic monitoring-based dosing records were included in the analysis. Age, body weight, and creatinine clearance were significant covariates on clearance, but only creatinine clearance was retained in the final models per stepwise selection. Sex was not a significant covariate on clearance. Tenofovir population pharmacokinetic parameter estimates and the precisions of the parameters from the two final models were comparable with the point estimates of the parameters, differing from 0% to 35%, and bootstrap confidence intervals widely overlapped. These findings indicate that PRDI was sufficient for population pharmacokinetic model development in this study, with a high level of adherence per multiple measures.

scholarly journals Population Pharmacokinetic Model for Intravenous ASN100 in Healthy Subjects

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S529-S529
Author(s):  
Scott A Van Wart ◽  
Christopher Stevens ◽  
Zoltan Magyarics ◽  
Steven A Luperchio ◽  
Paul G Ambrose
Keyword(s):  
Healthy Subjects ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic

scholarly journals Pharmacokinetics and Pharmacogenetics of Cyclophosphamide in a Neonate and Infant Childhood Cancer Patient Population

2021 ◽  
Vol 14 (3) ◽  
pp. 272
Author(s):  
Shelby Barnett ◽  
Julie Errington ◽  
Julieann Sludden ◽  
David Jamieson ◽  
Vianney Poinsignon ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Childhood Cancer ◽  
Patient Population ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Drug Clearance ◽  
Current Data ◽  
Population Pharmacokinetic ◽  
Older Children ◽  
Patient Groups

Infants and young children represent an important but much understudied childhood cancer patient population. The pharmacokinetics and pharmacogenetics of the widely used anticancer prodrug cyclophosphamide were investigated in children <2 years of age. Concentrations of cyclophosphamide and selected metabolites were determined in patients administered cyclophosphamide at doses ranging from 100–1500 mg/m2 (5–75 mg/kg), with various infusion times as determined by the standard treatment regimen that each patient was receiving. Polymorphisms in genes including CYP2B6 and CYP2C19 were investigated. Data generated for cyclophosphamide were analysed using a previously published population pharmacokinetic model. Cyclophosphamide pharmacokinetics was assessed in 111 samples obtained from 25 patients ranging from 4–23 months of age. The average cyclophosphamide clearance for the patients was 46.6 mL/min/m2 (ranging from 9.4–153 mL/min/m2), with marked inter-patient variability observed (CV 41%). No significant differences in cyclophosphamide clearance or exposure (AUC) were observed between patient groups as separated by age or body weight. However, marked differences in drug clearance and metabolism were noted between the current data in children <2 years of age and recently published results from a comparable study conducted by our group in older children, which reported significantly lower cyclophosphamide clearance values and metabolite exposures using the same population pharmacokinetic model for analysis. Whilst this study demonstrates no significant differences in cyclophosphamide clearance in patients <2 years, it highlights large differences in dosing protocols across tumour types. Furthermore, the study suggests marked differences in cyclophosphamide clearance in children less than two years of age as compared to older patients.

scholarly journals Novel Population Pharmacokinetic Model for Linezolid in Critically Ill Patients and Evaluation of the Adequacy of the Current Dosing Recommendation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 54 ◽  
Author(s):  
Amaia Soraluce ◽  
Helena Barrasa ◽  
Eduardo Asín-Prieto ◽  
Jose Ángel Sánchez-Izquierdo ◽  
Javier Maynar ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Standard Dose ◽  
Compartment Model ◽  
Antimicrobial Treatment ◽  
Population Pharmacokinetic ◽  
Renal Replacement Therapies ◽  
Continuous Renal Replacement Therapies

Antimicrobial treatment in critically ill patients remains challenging. The aim of this study was to develop a population pharmacokinetic model for linezolid in critically ill patients and to evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and effluent samples were drawn after linezolid administration at defined time points, and linezolid levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3. The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated (AUC24/MIC > 80 and 100% T>MIC). A two-compartment model best described the pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose of linezolid did not cover infections caused by pathogens with MIC ≥ 2 mg/L. Continuous infusion may be an alternative, especially when renal function is preserved.

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