Population pharmacokinetic model for adherence evaluation using lamivudine concentration monitoring.
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.
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Chao
C
Zhang
Paolo
P
Denti
Jan-Stefan
JS
van der Walt
Yuan
Y
Ren
Peter
P
Smith
Mats O
MO
Karlsson
Helen
H
McIlleron
D000042:Absorption; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics*; D044966:Anti-Retroviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002675:Child, Preschool; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics*; D008954:Models, Biological
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D019259:Lamivudine