Population pharmacokinetic model for adherence evaluation using lamivudine concentration monitoring

• Published in: Therapeutic drug monitoring Vol. 34; no. 4; p. 481
• Main Authors: Zhang, Chao, Denti, Paolo, van der Walt, Jan-Stefan, Ren, Yuan, Smith, Peter, Karlsson, Mats O, McIlleron, Helen
• Format: Journal Article
• Language: English
• Published: United States 01.08.2012
• Subjects: Absorption; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacokinetics; Anti-Retroviral Agents - blood; Anti-Retroviral Agents - pharmacokinetics; Area Under Curve; Child, Preschool; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - metabolism; Humans; Infant; Lamivudine - blood; Lamivudine - pharmacokinetics; Models, Biological
• ISSN: 1536-3694
• DOI: 10.1097/FTD.0b013e31825c6067

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. 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. 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. Lamivudine concentration measurement can be used to assess recent treatment adherence.