ArticleThe Journal of antimicrobial chemotherapy2017
Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Pharmacogenetic predictors of nevirapine pharmacokinetics in Ghanaian children living with HIV with or without TB coinfection.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2021Trial
- Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention.The Journal of antimicrobial chemotherapy · 2021Trial
- Effect of Pregnancy on Unbound Raltegravir Concentrations in the ANRS 160 RalFe Trial.Antimicrobial agents and chemotherapy · 2020Article
- Ser100-Phosphorylated RORMolecular pharmacology · 2020Article
- Development of visual predictive checks accounting for multimodal parameter distributions in mixture models.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Population pharmacokinetic modeling of sustained release lithium in the serum, erythrocytes and urine of patients with bipolar disorder.European journal of clinical pharmacology · 2019Article
- Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants.The Journal of antimicrobial chemotherapy · 2017Article
- Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets.AIDS (London, England) · 2017Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 5 countries.
Funding
Abstract
objectivesTo characterize the effects of CYP2B6 polymorphisms, diurnal variation and demographic factors on nevirapine pharmacokinetics in African children.
methodsNon-linear mixed-effects modelling conducted in NONMEM 7.3 described nevirapine plasma concentration-time data from 414 children aged 0.3-15 years.
resultsNevirapine pharmacokinetics was best described using a one-compartment disposition model with elimination through a well-stirred liver model accounting for a first-pass effect and transit-compartment absorption. Intrinsic clearance was affected by diurnal variation (characterized using a cosine function with peak amplitude 29% at 12 noon) and CYP2B6 metabolizer status [extensive metabolizer (EM) 516GG|983TT, reference; intermediate metabolizer (IM) 516GT|983TT or 516GG|983TC, 17% lower; slow metabolizer (SM) 516TT|983TT or 516GT|983TC, 50% lower; ultra-slow metabolizer (USM) 516GG|983CC, 68% lower]. Age was found to affect pre-hepatic bioavailability: 31.7% lower at birth and increasing exponentially. Median (90% CI) evening C
conclusionsDiurnal variation does not greatly affect nevirapine exposure. However, when daily doses cannot be split equally, the larger dose should be given in the morning. To achieve homogeneous exposures, nevirapine doses for SM and USM should be reduced by 50%, and children weighing <6 kg with EM or IM metabolizer status should receive the same dose as children weighing 6-10 kg.
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