Population pharmacokinetic model for adherence evaluation using lamivudine concentration monitoring
Therapeutic Drug Monitoring
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory, Cape Town 7925, South Africa; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
BACKGROUND: Interpretation of antiretroviral drug concentration measurements could be aided by information about adherence to recent doses. We developed a population pharmacokinetic model of lamivudine in young children to propose reference lamivudine concentrations for evaluation of adherence to recent treatment doses. METHODS: The steady state pharmacokinetics of lamivudine were evaluated in 68 young HIV-infected children receiving antiretroviral treatment twice daily. A population pharmacokinetic analysis was conducted using NONMEM 7. RESULTS: A 2-compartment model with transit absorption best described lamivudine pharmacokinetics. After adjustment for maturation and body weight (using allometric scaling), the variability of clearance was small, hence simulations could accurately predict lamivudine concentrations. Higher lamivudine trough concentrations were detected before the morning dose, possibly owing to slower overnight clearance. Reference values for lamivudine concentrations that can be used to evaluate adherence to recent doses are proposed. CONCLUSIONS: Lamivudine concentration measurement can be used to assess recent treatment adherence. Copyright © 2012 by Lippincott Williams & Wilkins.
lamivudine; lopinavir plus ritonavir; allometry; article; body weight; child; compartment model; drug absorption; drug blood level; drug clearance; drug monitoring; highly active antiretroviral therapy; human; Human immunodeficiency virus infection; infant; major clinical study; patient compliance; preschool child; priority journal; steady state; Absorption; Anti-HIV Agents; Anti-Retroviral Agents; Area Under Curve; Child, Preschool; HIV Infections; Humans; Infant; Lamivudine; Models, Biological