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.
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-infectedchildren 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.
Authors: Esther J H Janssen; Diane E T Bastiaans; Pyry A J Välitalo; Annemarie M C van Rossum; Evelyne Jacqz-Aigrain; Hermione Lyall; Catherijne A J Knibbe; David M Burger Journal: Br J Clin Pharmacol Date: 2017-02-14 Impact factor: 4.335
Authors: Sarah K Wendel; Caroline E Mullis; Susan H Eshleman; Joel N Blankson; Richard D Moore; Jeanne C Keruly; Ron Brookmeyer; Thomas C Quinn; Oliver Laeyendecker Journal: PLoS One Date: 2013-02-20 Impact factor: 3.240