ArticleBritish journal of clinical pharmacology2012
Population pharmacokinetics and maximum a posteriori probability Bayesian estimator of abacavir: application of individualized therapy in HIV-infected infants and toddlers.
Article in British journal of clinical pharmacology, 2012. 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, 11 citations in OpenAlex.
- Population pharmacokinetics of abacavir and lamivudine in severely malnourished human immunodeficiency virus-infected children in relation to treatment outcomes.British journal of clinical pharmacology · 2019Trial
- Abacavir Drug Exposures in African Children Under 14 kg Using Pediatric Solid Fixed Dose Combinations According to World Health Organization Weight Bands.Journal of the Pediatric Infectious Diseases Society · 2023Article
- Suggestions for Model-Informed Precision Dosing to Optimize Neonatal Drug Therapy.Journal of clinical pharmacology · 2019Review
- Integrated semi-physiological pharmacokinetic model for both sunitinib and its active metabolite SU12662.British journal of clinical pharmacology · 2015Article
- Population pharmacokinetics of abacavir in pregnant women.Antimicrobial agents and chemotherapy · 2014Article
- Advances in pediatric pharmacology, therapeutics, and toxicology.Advances in pediatrics · 2014Review
- Population pharmacokinetics of abacavir in infants, toddlers and children.British journal of clinical pharmacology · 2013Article
- Practical Considerations For Developing Nucleoside Reverse Transcriptase Inhibitors.Drug discovery today. Technologies · 2012Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 4 countries.
Funding
Abstract
what is already known about this subjectAbacavir is used to treat HIV infection in both adults and children. The recommended paediatric dose is 8 mg kg(-1) twice daily up to a maximum of 300 mg twice daily. Weight was identified as the central covariate influencing pharmacokinetics of abacavir in children. WHAT THIS STUDY ADDS: A population pharmacokinetic model was developed to describe both once and twice daily pharmacokinetic profiles of abacavir in infants and toddlers. Standard dosage regimen is associated with large interindividual variability in abacavir concentrations. A maximum a posteriori probability Bayesian estimator of AUC(0-) (t) based on three time points (0, 1 or 2, and 3 h) is proposed to support area under the concentration-time curve (AUC) targeted individualized therapy in infants and toddlers.
aimsTo develop a population pharmacokinetic model for abacavir in HIV-infected infants and toddlers, which will be used to describe both once and twice daily pharmacokinetic profiles, identify covariates that explain variability and propose optimal time points to optimize the area under the concentration-time curve (AUC) targeted dosage and individualize therapy.
methodsThe pharmacokinetics of abacavir was described with plasma concentrations from 23 patients using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment model with first-order absorption and elimination was developed. The final model was validated using bootstrap, visual predictive check and normalized prediction distribution errors. The Bayesian estimator was validated using the cross-validation and simulation-estimation method.
resultsThe typical population pharmacokinetic parameters and relative standard errors (RSE) were apparent systemic clearance (CL) 13.4 () h−1 (RSE 6.3%), apparent central volume of distribution 4.94 () (RSE 28.7%), apparent peripheral volume of distribution 8.12 () (RSE14.2%), apparent intercompartment clearance 1.25 () h−1 (RSE 16.9%) and absorption rate constant 0.758 h−1 (RSE 5.8%). The covariate analysis identified weight as the individual factor influencing the apparent oral clearance: CL = 13.4 × (weight/12)1.14. The maximum a posteriori probability Bayesian estimator, based on three concentrations measured at 0, 1 or 2, and 3 h after drug intake allowed predicting individual AUC0–t.
conclusionsThe population pharmacokinetic model developed for abacavir in HIV-infected infants and toddlers accurately described both once and twice daily pharmacokinetic profiles. The maximum a posteriori probability Bayesian estimator of AUC(0-) (t) was developed from the final model and can be used routinely to optimize individual dosing.
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