Trial reportAntimicrobial agents and chemotherapy2010
Population pharmacokinetic-pharmacogenetic study of nevirapine in HIV-infected Cambodian patients.
Trial report in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Genetics of Nevirapine Metabolic Pathways at Steady State in HIV-Infected Cambodians.Antimicrobial agents and chemotherapy · 2017Trial
- Population pharmacokinetics of nevirapine in Malaysian HIV patients: a non-parametric approach.European journal of clinical pharmacology · 2016Trial
- Clinical and genetic determinants of plasma nevirapine exposure following an intrapartum dose to prevent mother-to-child HIV transmission.The Journal of infectious diseases · 2013Trial
- Pharmacogenomics of Antiretroviral Drug Metabolism and Transport.Annual review of pharmacology and toxicology · 2021Review
- Adverse Drug Reactions Associated with CYP 2B6 Polymorphisms in HIV/AIDS-Treated Patients in Yaoundé, Cameroon.The application of clinical genetics · 2019Article
- Efficacy and safety of switching from nevirapine immediate-release twice daily to nevirapine extended-release once daily in virologically suppressed HIV-infected patients: a retrospective cohort study in Taiwan.BMC infectious diseases · 2017Article
- Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children.The Journal of antimicrobial chemotherapy · 2017Article
- Combined Analysis of Phase I and Phase II Data to Enhance the Power of Pharmacogenetic Tests.CPT: pharmacometrics & systems pharmacology · 2016Article
- Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations.Medicine · 2016Observational
- Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.PloS one · 2016Article
- Population pharmacokinetic model to analyze nevirapine multiple-peaks profile after a single oral dose.Journal of pharmacokinetics and pharmacodynamics · 2014Article
- Population pharmacokinetic and pharmacogenetic analysis of nevirapine in hypersensitive and tolerant HIV-infected patients from Malawi.Antimicrobial agents and chemotherapy · 2014Article
- Clinical pharmacokinetics of antiretroviral drugs in older persons.Expert opinion on drug metabolism & toxicology · 2013Review
- Pharmacokinetics of phase I nevirapine metabolites following a single dose and at steady state.Antimicrobial agents and chemotherapy · 2013Article
- Multiple genetic variants predict steady-state nevirapine clearance in HIV-infected Cambodians.Pharmacogenetics and genomics · 2012Article
- Nevirapine exposure with WHO pediatric weight band dosing: enhanced therapeutic concentrations predicted based on extensive international pharmacokinetic experience.Antimicrobial agents and chemotherapy · 2012Article
- Integration of data from multiple sources for simultaneous modelling analysis: experience from nevirapine population pharmacokinetics.British journal of clinical pharmacology · 2012Article
- Clinical perspectives on human genetic screening to prevent nevirapine toxicity.Personalized medicine · 2012Article
- Influence of CYP2B6 and ABCB1 SNPs on nevirapine plasma concentrations in Burundese HIV-positive patients using dried sample spot devices.British journal of clinical pharmacology · 2012Article
- Covariate pharmacokinetic model building in oncology and its potential clinical relevance.The AAPS journal · 2012Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aims of this ANRS12154 open-label, single-center, multiple-dose pharmacokinetic study were to characterize nevirapine pharmacokinetics in a Cambodian population of HIV-infected patients and to identify environmental and genetic factors of variability, focusing on the CYP2B6, CYP3A5, and ABCB1 (MDR1) genes. A total of 170 Cambodian HIV-infected patients were included. Nevirapine trough concentrations were measured after 18 and 36 months of starting antiretroviral treatment and in samples drawn during a dosing interval in a subset of 10 patients. All data were analyzed by nonlinear mixed-effects modeling. The effect of covariates was investigated using the population pharmacokinetic model. Patients carrying homozygous loss-of-function alleles CYP3A5 6986A>G, CYP2B6 516G>T, CYP2B6 1459C>T, and ABCB1 3435C>T represent 42.4%, 9.2%, 0%, and 18% of the population, respectively. The median nevirapine trough concentrations did not differ after 18 and 36 months of treatment (5,705 ng/ml [range, ≤50 to 13,871] and 5,709 ng/ml [range, ≤50 to 15,422], respectively). Interpatient and intrapatient variabilities of nevirapine apparent clearance were 28% and 17%, respectively. CYP2B6 516G>T and creatinine clearance were found to significantly affect nevirapine apparent clearance. The estimated nevirapine apparent clearances were 2.95 liters/h, 2.62 liters/h, and 1.86 liters/h for CYP2B6 516GG, CYP2B6 516GT, and CYP2B6 516TT genotypes, respectively. The impact of creatinine clearance was small. This study demonstrates that 95% of the patients had sustained nevirapine exposure well above the 3,000-ng/ml threshold. Nevirapine clearance was shown to be affected by CYP2B6 516G>T genetic polymorphism and creatinine clearance, although this explained only part of the interpatient variability, which remains low compared to that for other antiretroviral drugs.
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