Lamivudine dosing for preterm infants exposed to HIV: a population pharmacokinetic modelling and simulation study

Abstract Objectives To develop a pragmatic twice daily lamivudine dosing strategy for preterm infants from 24 to 37 completed weeks of gestation. Methods Data were combined from eight pharmacokinetic studies in neonates and infants receiving lamivudine oral solution. A population pharmacokinetic mod...

Full description

Saved in:
Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2024-10, Vol.79 (10), p.2570-2574
Main Authors: Bekker, Adrie, Capparelli, Edmund V, Mirochnick, Mark, Clarke, Diana F, Cotton, Mark F, Shapiro, Roger, McCarthy, Katie, Moye, Jack, Violari, Avy, Chokephaibulkit, Kulkanya, Abrams, Elaine, Penazzato, Martina, Ruel, Theodore D, Cressey, Tim R
Format: Article
Language:English
Subjects:
Anti-HIV Agents - administration & dosage
Anti-HIV Agents - pharmacokinetics
Anti-HIV Agents - therapeutic use
Computer Simulation
Female
Gestational Age
HIV Infections - drug therapy
Humans
Infant
Infant, Newborn
Infant, Premature
Lamivudine - administration & dosage
Lamivudine - pharmacokinetics
Male
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Objectives To develop a pragmatic twice daily lamivudine dosing strategy for preterm infants from 24 to 37 completed weeks of gestation. Methods Data were combined from eight pharmacokinetic studies in neonates and infants receiving lamivudine oral solution. A population pharmacokinetic model was developed using non-linear mixed effects regression. Different lamivudine dosing strategies, stratified by gestational age at birth (GA) bands, were simulated in a virtual population of preterm infants, aimed at maintaining lamivudine drug exposures (AUC0-12) within a reference target range of 2.95 to 13.25 µg·h/mL, prior to switching to WHO-weight band doses when ≥4 weeks of age and weighing ≥3 kg. Results A total of 154 infants (59% female) contributed 858 lamivudine plasma concentrations. Median (range) GA at birth was 38 (27–41) weeks. At the time of first pharmacokinetic sampling infants were older with median postnatal age (PNA) of 6.3 (0.52–26.6) weeks. Lamivudine concentrations were described by a one-compartment model, with CL/F and V/F allometrically scaled to weight. Maturation of CL/F was described using an Emax model based on PNA. CL/F was also adjusted on GA to allow extrapolation for extreme prematurity. Simulations predicted an optimal lamivudine dosing for infants GA ≥24 to
ISSN:0305-7453
1460-2091
1460-2091
DOI:10.1093/jac/dkae259