ArticleBritish journal of clinical pharmacology2016
The impact of genetic polymorphisms on the pharmacokinetics of efavirenz in African children.
Article in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Influence of CYP2B6 activity score on the pharmacokinetics and safety of single dose efavirenz in healthy volunteers.The pharmacogenomics journal · 2020Trial
- Efavirenz metabolism and CNS toxicity in Ugandan children: impact of CYP2B6 genotype and plasma metabolite profiles.Frontiers in pharmacology · 2026Article
- Population Pharmacokinetic-Pharmacogenetic (PopPK-PGx) Model of Efavirenz in HIV-1-Infected Patients.Cureus · 2025Article
- Sub- and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study.British journal of clinical pharmacology · 2025Article
- Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid.Southern African journal of HIV medicine · 2025Article
- Causal Inference for Continuous Multiple Time Point Interventions.Statistics in medicine · 2024Article
- Determining Targets for Antiretroviral Drug Concentrations: A Causal Framework Illustrated With Pediatric Efavirenz Data From the CHAPAS-3 Trial.Pharmacoepidemiology and drug safety · 2024Article
- Genetic and non-genetic factors influencing efavirenz population pharmacokinetics among human immunodeficiency virus-1-infected children in Ethiopia.CPT: pharmacometrics & systems pharmacology · 2023Article
- Pharmacogenetic Aspects of Drug Metabolizing Enzymes and Transporters in Pediatric Medicine: Study Progress, Clinical Practice and Future Perspectives.Paediatric drugs · 2023Review
- Pharmacogenetics ofJournal of personalized medicine · 2022Article
- Concentration-response relationships of dolutegravir and efavirenz with weight change after starting antiretroviral therapy.British journal of clinical pharmacology · 2022Article
- Pharmacogenetics of Praziquantel Metabolism: Evaluating the Cytochrome P450 Genes of Zimbabwean Patients During a Schistosomiasis Treatment.Frontiers in genetics · 2022Article
- Evaluation of the estimation and classification performance of NONMEM when applying mixture model for drug clearance.CPT: pharmacometrics & systems pharmacology · 2021Article
- The Pharmacogenetics of Efavirenz Metabolism in Children: The Potential Genetic and Medical Contributions to Child Development in the Context of Long-Term ARV Treatment.New directions for child and adolescent development · 2020Review
- Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir.Antimicrobial agents and chemotherapy · 2020Article
- New Directions for the Consideration of HIV: Heterogeneity and the Cognition of Time.New directions for child and adolescent development · 2020Article
- Population pharmacokinetics of efavirenz in HIV and TB/HIV coinfected children: the significance of genotype-guided dosing.The Journal of antimicrobial chemotherapy · 2019Article
- Establishing Dosing Recommendations for Efavirenz in HIV/TB-Coinfected Children Younger Than 3 Years.Journal of acquired immune deficiency syndromes (1999) · 2019Article
- Optimizing Pediatric Dosing Recommendations and Treatment Management of Antiretroviral Drugs Using Therapeutic Drug Monitoring Data in Children Living With HIV.Therapeutic drug monitoring · 2019Review
- A Comparison of Plasma Efavirenz and Tenofovir, Dried Blood Spot Tenofovir-Diphosphate, and Self-Reported Adherence to Predict Virologic Suppression Among South African Women.Journal of acquired immune deficiency syndromes (1999) · 2019Article
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 5 countries.
Funding
Abstract
aimsUsing a model-based approach, the efavirenz steady-state pharmacokinetics in African children is characterized, quantifying demographic and genotypic effects on the drug's disposition. Simulations are also conducted allowing prediction of optimized doses of efavirenz in this population.
methodsWe modelled the steady-state population pharmacokinetics of efavirenz in Ugandan and Zambian children using nonlinear mixed-effects modelling. Individual mid-dose efavirenz concentrations were derived and simulations explored genotype-based dose optimization strategies.
resultsA two-compartment model with absorption through transit compartments well described 2086 concentration-time points in 169 children. The combined effect of single nucleotide polymorphisms (SNPs) 516G>T and 983T>C explained 44.5% and 14.7% of the variability in efavirenz clearance and bioavailability, respectively. The detected frequencies of composite CYP2B6 genotype were 0.33 for 516GG|983TT, 0.35 for 516GT|983TT, 0.06 for 516GG|983TC, 0.18 for 516TT|983TT, 0.07 516GT|983TC and 0.01 for 516GG|983CC. The corresponding estimated clearance rates were 6.94, 4.90, 3.93, 1.92, 1.36, and 0.74 l h(-1) for a 15.4 kg child and median (95% CI) observed mid-dose concentrations 1.55 (0.51-2.94), 2.20 (0.97-4.40), 2.03 (1.19-4.53), 7.55 (2.40-14.74), 7.79 (3.66-24.59) and 18.22 (11.84-22.76) mg l(-1) , respectively. Simulations showed that wild-type individuals had exposures at the bottom of therapeutic range, while slower metabolizers were overexposed.
conclusionsDosage guidelines for African children should take into consideration the combined effect of SNPs CYP2B6 516G>T and 983T>C.
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