Zidovudine kinetics in the pregnant baboon

Marianne Garland, Hazel H. Szeto, Salha S. Daniel, Pamela J. Tropper, Michael M. Myers, Raymond I. Stark

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The devastating impact of human immunodeficiency virus (HIV) infection during pregnancy has made the pharmacologic evaluation of potentially therapeutic agents of high priority. The results presented here are the maternal pharmacokinetics from a series of experiments to delineate more clearly the complex maternal-fetal pharmacokinetics and the effects of AZT in the chronically instrumented maternal and fetal baboon during both steady state intravenous infusion and oral bolus dosage regimens. Two results of major clinical importance were found. First, during pregnancy, both the clearance and volume of distribution of AZT were increased. Plasma clearance in the pregnant animals was 51 ± 10 ml/min/kg compared with 37 ± 2 ml/min/kg in the nonpregnant animals, and steady state volume of distribution was 3.7 ± 1.21/kg compared with 2.2 ± 0.61/kg. Second, with continuous intravenous infusion plasma drug concentrations were easily maintained in the therapeutic range, whereas with oral administration plasma concentration fell below therapeutic levels within 2 h of the dose being given. Because maternal plasma concentrations are a major determinant of drug concentration achieved in the fetus, an understanding of drug kinetics in pregnancy is of vital importance when making recommendations regarding optimal drug therapy during pregnancy to maximize the beneficial effect-the prevention of HIV infection in children.

Original languageEnglish (US)
Pages (from-to)117-127
Number of pages11
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume11
Issue number2
DOIs
Publication statusPublished - Jan 1 1996

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Keywords

  • Baboon
  • Pharmacokinetics
  • Pregnancy
  • Primate
  • Zidovudine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

Cite this

Garland, M., Szeto, H. H., Daniel, S. S., Tropper, P. J., Myers, M. M., & Stark, R. I. (1996). Zidovudine kinetics in the pregnant baboon. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 11(2), 117-127. https://doi.org/10.1097/00042560-199602010-00002