ArticleAntimicrobial agents and chemotherapy2009
Influence of the cytochrome P450 2B6 genotype on population pharmacokinetics of efavirenz in human immunodeficiency virus patients.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 73 citations in OpenAlex.
- Population Pharmacokinetic Modeling To Estimate the Contributions of Genetic and Nongenetic Factors to Efavirenz Disposition.Antimicrobial agents and chemotherapy · 2017Trial
- Population pharmacogenetic-based pharmacokinetic modeling of efavirenz, 7-hydroxy- and 8-hydroxyefavirenz.Journal of clinical pharmacology · 2014Trial
- Influence of CYP2B6 516G>T polymorphism and interoccasion variability (IOV) on the population pharmacokinetics of efavirenz in HIV-infected South African children.European journal of clinical pharmacology · 2012Trial
- Population pharmacokinetic/pharmacogenetic model for optimization of efavirenz therapy in Caucasian HIV-infected patients.Antimicrobial agents and chemotherapy · 2011Trial
- Population Pharmacokinetic-Pharmacogenetic (PopPK-PGx) Model of Efavirenz in HIV-1-Infected Patients.Cureus · 2025Article
- A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant.Pharmaceutics · 2024Article
- Genetic and non-genetic factors influencing efavirenz population pharmacokinetics among human immunodeficiency virus-1-infected children in Ethiopia.CPT: pharmacometrics & systems pharmacology · 2023Article
- Influence ofPharmacogenomics and personalized medicine · 2021Article
- Prediction of the exposure to a 400-mg daily dose of efavirenz in pregnancy: is this dose adequate in extensive metabolisers of CYP2B6?European journal of clinical pharmacology · 2020Article
- Occurrence of CYP2B6 516G>T polymorphism in patients with ARV-associated hepatotoxicity.Molecular genetics & genomic medicine · 2019Article
- Long-term efavirenz pharmacokinetics is comparable between Tanzanian HIV and HIV/Tuberculosis patients with the same CYP2B6*6 genotype.Scientific reports · 2018Article
- Efavirenz and Metabolites in Cerebrospinal Fluid: Relationship with CYP2B6 c.516G→T Genotype and Perturbed Blood-Brain Barrier Due to Tuberculous Meningitis.Antimicrobial agents and chemotherapy · 2016Article
- The impact of genetic polymorphisms on the pharmacokinetics of efavirenz in African children.British journal of clinical pharmacology · 2016Article
- Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation.BMC infectious diseases · 2016Article
- CYP2B6*6, CYP2B6*18, Body weight and sex are predictors of efavirenz pharmacokinetics and treatment response: population pharmacokinetic modeling in an HIV/AIDS and TB cohort in Zimbabwe.BMC pharmacology & toxicology · 2015Article
- An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3'-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients.Frontiers in genetics · 2015Article
- Low level of efavirenz in HIV-1-infected Thai adults is associated with the CYP2B6 polymorphism.Infection · 2014Article
- Impact of CYP polymorphisms, ethnicity and sex differences in metabolism on dosing strategies: the case of efavirenz.European journal of clinical pharmacology · 2014Review
- Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype dependent.The pharmacogenomics journal · 2014Article
- CYP2B6 18492T->C polymorphism compromises efavirenz concentration in coinfected HIV and tuberculosis patients carrying CYP2B6 haplotype *1/*1.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A population pharmacokinetic model for efavirenz has been developed from therapeutic drug monitoring data in human immunodeficiency virus (HIV)-positive patients by using a nonlinear mixed-effect model. The efavirenz plasma concentrations (n = 375) of 131 patients were analyzed using high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were estimated according to a one-compartment model. The effects of sex, age, total body weight, height, body mass index, and HIV treatment were analyzed. In a subgroup of 32 patients, genetic polymorphisms of the cytochrome P450 2B6 gene (CYP2B6), CYP3A4, and MDR1 were also investigated. Efavirenz oral clearance and the apparent volume of distribution were 9.50 liters/h and 311 liters, respectively. The model included only the effect of CYP2B6 polymorphisms on efavirenz clearance; this covariate reduced the intersubject variability of clearance by about 27%. Patients showing G/T and T/T CYP2B6 polymorphisms exhibited efavirenz clearances that were about 50% and 75% lower than those observed in the patients without these polymorphisms (G/G). Accordingly, to obtain EFV steady-state concentrations within the therapeutic range (1 to 4 mg/liter), it would be advisable to implement a gradual reduction in dose to 400 or 200 mg/day for patients that are intermediate or poor metabolizers, respectively. However, the remaining interindividual variability observed in the pharmacokinetic parameters of the model highlights the need for dose individualization to avoid inadequate exposure to efavirenz and suggests that these recommended doses be used with caution and confirmed by therapeutic drug monitoring and clinical efficacy. The population model can be implemented in pharmacokinetic clinical software for dosage optimization by using the Bayesian approach.
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