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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Population pharmacokinetics and maximum a posteriori probability Bayesian estimator of abacavir: Application of individualized therapy in HIV-infected infants and toddlers
British Journal of Clinical Pharmacology, Volume 73, No. 4, Year 2012
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Description
AIMS To 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. METHODS The 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. RESULTS The typical population pharmacokinetic parameters and relative standard errors (RSE) were apparent systemic clearance (CL) 13.4lh -1 (RSE 6.3%), apparent central volume of distribution 4.94l (RSE 28.7%), apparent peripheral volume of distribution 8.12l (RSE14.2%), apparent intercompartment clearance 1.25lh -1 (RSE 16.9%) and absorption rate constant 0.758h -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 3h after drug intake allowed predicting individual AUC 0-t. CONCLUSIONS The 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. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
Authors & Co-Authors
Della Pasqua, Oscar E.
Netherlands, Leiden
Universiteit Leiden
United Kingdom, Brentford
Glaxosmithkline Plc.
Burger, David M.
Netherlands, Nijmegen
Radboud Universiteit
Netherlands, Nijmegen
Radboud University Medical Center
Jacqz-Aigrain, Évelyne M.
France, Paris
Université Paris Cité
France, Paris
Inserm
Aboulker, Jean Pierre
Unknown Affiliation
Brothers, Cindy H.
Unknown Affiliation
Burger, David Marinus
Unknown Affiliation
Compagnucci, Alexandra
Unknown Affiliation
Giaquinto, Carlo
Unknown Affiliation
Gibb, Diana M.
Unknown Affiliation
Krivine, Anne
Unknown Affiliation
Faye, Albert
France, Paris
Hôpital Robert-debré Ap-hp
Damond, Florence
France, Paris
Hôpital Robert-debré Ap-hp
Wintergerst, Uwe
Unknown Affiliation
Notheis, Gundula
Unknown Affiliation
Giaquinto, Carlo
Italy, Padua
Università Degli Studi Di Padova
Zanchetta, Marisa
Italy, Padua
Università Degli Studi Di Padova
De Rossi, Anita
Italy, Padua
Università Degli Studi Di Padova
Ramos, José Tomás
Spain, Getafe
Hospital Universitario de Getafe
Navarro-Gõmez, Marisa Luisa
Spain, Madrid
Hospital General Universitario Gregorio Marañón
Lyall, Hermione
United Kingdom, London
Imperial College Healthcare Nhs Trust
Tudor-Williams, Gareth
United Kingdom, London
Imperial College Healthcare Nhs Trust
Foster, Caroline J.
United Kingdom, London
Imperial College Healthcare Nhs Trust
Kaye, Steve
United Kingdom, London
Imperial College Healthcare Nhs Trust
Patel, Darshana
United Kingdom, London
Imperial College Healthcare Nhs Trust
Welch, Steven B.
United Kingdom, Birmingham
Heartlands Hospital
Smit, Erasmus J.
United Kingdom, Birmingham
Heartlands Hospital
Lewis, Paul O.
United Kingdom, Coventry
University Hospitals Coventry and Warwickshire Nhs Trust
McMaster, Paddy
United Kingdom, Stoke-on-trent
Royal Stoke University Hospital
Morris, Lynn G.
United Kingdom, London
Ucl Medical School
Grant, Paul R.
United Kingdom, London
Ucl Medical School
Kirk, Stuart
United Kingdom, London
Ucl Medical School
Statistics
Citations: 11
Authors: 31
Affiliations: 20
Identifiers
Doi:
10.1111/j.1365-2125.2011.04121.x
ISSN:
13652125
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Cross Sectional Study