Display Settings:

Format

Send to:

Choose Destination
Antimicrob Agents Chemother. 2007 Dec;51(12):4297-302. Epub 2007 Sep 24.

Population pharmacokinetics of lamivudine in human immunodeficiency virus-exposed and -infected infants.

Author information

  • 1Division of Pharmacology and Drug Discovery, Pediatric Pharmacology Research Unit, University of California San Diego, MC 8214, San Diego, CA 92103-8214, USA. atremoul@ucsd.edu

Abstract

This study aimed to determine lamivudine disposition in infants and to construct an appropriate dose adjustment for age, given the widespread use of lamivudine for both the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) and the treatment of HIV-infected infants. Using a pooled-population approach, the pharmacokinetics of lamivudine in HIV-exposed or -infected infants from four Pediatric AIDS Clinical Trials Group studies were assessed. Ninety-nine infants provided 559 plasma samples for measurement of lamivudine concentrations. All infants received combination antiretroviral therapy including lamivudine dosed at 2 mg/kg of body weight every 12 h (q12h) for the first 4 to 6 weeks of life and at 4 mg/kg q12h thereafter. Lamivudine's apparent clearance was 0.25 liter/h/kg at birth, doubling by 28 days. In the final model, age and weight were the only significant covariates for lamivudine clearance. While lamivudine is predominantly renally eliminated, the serum creatinine level was not an independent covariate in the final model, possibly because it was confounded by age. Inclusion of interoccasion variability for bioavailability improved the individual subject clearance prediction over the age range studies. Simulations based on the final model predicted that by the age of 4 weeks, 90% of infant lamivudine concentrations with the standard 2 mg/kg dose of lamivudine fell below the adult median concentration. This population pharmacokinetic analysis affirms that adjusting the dose of lamivudine from 2 mg/kg to 4 mg/kg q12 h at the age of 4 weeks for infants with normal maturation of renal function will provide optimal lamivudine exposure, potentially contributing to more successful therapy.

PMID:
17893155
[PubMed - indexed for MEDLINE]
PMCID:
PMC2168008
Free PMC Article

Images from this publication.See all images (5)Free text

FIG. 1.
FIG. 2.
FIG. 3.
FIG. 4.
FIG. 5.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk