Lamivudine dosing for preterm infants exposed to HIV: a population pharmacokinetic modelling and simulation study
Issued Date
2024-10-01
Resource Type
eISSN
14602091
Scopus ID
2-s2.0-85205525017
Pubmed ID
39092932
Journal Title
The Journal of antimicrobial chemotherapy
Volume
79
Issue
10
Start Page
2570
End Page
2574
Rights Holder(s)
SCOPUS
Bibliographic Citation
The Journal of antimicrobial chemotherapy Vol.79 No.10 (2024) , 2570-2574
Suggested Citation
Bekker A., Capparelli E.V., Mirochnick M., Clarke D.F., Cotton M.F., Shapiro R., McCarthy K., Moye J., Violari A., Chokephaibulkit K., Abrams E., Penazzato M., Ruel T.D., Cressey T.R. Lamivudine dosing for preterm infants exposed to HIV: a population pharmacokinetic modelling and simulation study. The Journal of antimicrobial chemotherapy Vol.79 No.10 (2024) , 2570-2574. 2574. doi:10.1093/jac/dkae259 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101550
Title
Lamivudine dosing for preterm infants exposed to HIV: a population pharmacokinetic modelling and simulation study
Author's Affiliation
Siriraj Hospital
Department of Pediatrics
FHI 360
Botswana Harvard AIDS Institute Partnership
Harvard T.H. Chan School of Public Health
Organisation Mondiale de la Santé
University of California, San Francisco
National Institute of Child Health and Human Development (NICHD)
University of the Witwatersrand, Johannesburg
Mailman School of Public Health
Boston University Chobanian & Avedisian School of Medicine
Boston Medical Center
Stellenbosch University
Chiang Mai University
Department of Pediatrics
FHI 360
Botswana Harvard AIDS Institute Partnership
Harvard T.H. Chan School of Public Health
Organisation Mondiale de la Santé
University of California, San Francisco
National Institute of Child Health and Human Development (NICHD)
University of the Witwatersrand, Johannesburg
Mailman School of Public Health
Boston University Chobanian & Avedisian School of Medicine
Boston Medical Center
Stellenbosch University
Chiang Mai University
Corresponding Author(s)
Other Contributor(s)
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 <30 weeks of 2 mg/kg twice daily from birth until weighing 3 kg; and for GA ≥30 to <37 weeks, 2 mg/kg twice daily for the first 4 weeks of life, followed by 4 mg/kg twice daily until weighing 3 kg. CONCLUSIONS: Model-based predictions support twice daily pragmatic GA band dosing of lamivudine for preterm infants, but clinical validation is warranted.