Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/51832
Title: Developmental pharmacokinetic changes of lamivudine in infants and children
Authors: Adriana H. Tremoulet
Mina Nikanjam
Tim R. Cressey
Kulkanya Chokephaibulkit
Ross McKinney
Mark Mirochnick
Edmund V. Capparelli
Keywords: Medicine
Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Dec-2012
Abstract: Lamivudine is a nucleoside reverse transcriptase inhibitor widely used in infants and children in combination antiretroviral therapy to treat human immunodeficiency virus (HIV) infection. Developmental changes in lamivudine pharmacokinetic disposition were assessed by combining data from 7 studies of lamivudine (Pediatric AIDS Clinical Trials Group 300, 353, 356, 358, 386, 1056, and 1069) representing subjects across the pediatric age continuum. A population pharmacokinetic model was developed to identify factors that influence lamivudine disposition. Age and Thai race were independent predictors of apparent clearance (CL/F), whereas the use of a fixed drug combination formulation (GPO-VIR) was an independent predictor of bioavailability, with CL/F more than doubling from birth to adolescence. Serum creatinine was not associated with CL/F. Monte Carlo simulations were used to compare the lamivudine exposure achieved with World Health Organization (WHO) weight band and Food and Drug Administration (FDA) label dosing recommendations. WHO dosing yielded higher exposure during the first few months of life, but this difference was less pronounced between 6 months and 14 years of age. Overall, both FDA and WHO dosing provided similar AUC values to those previously reported in HIV-infected adults. Lamivudine WHO weight band dosing results in therapeutic exposure in infants and children and may improve drug dosing in resource-limited countries. © 2012 The Author(s).
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84868629145&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/51832
ISSN: 15524604
00912700
Appears in Collections:CMUL: Journal Articles

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