Implications of the kinetics of zidovudine in the pregnant baboon following oral administration

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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Zidovudine (ZDV) therapy in pregnancy reduces mother-to-child transmission of HIV. The action of ZDV in the fetus is thought to be an important contributor to efficacy. Previous research in primates has demonstrated that continuous infusion of ZDV to the mother leads to sustained plasma concentrations in the fetus; however, it has not been determined what concentrations of ZDV are achieved in the fetus following oral administration. The pharmacokinetics of drug distribution to the fetus following oral administration of a 100-mg dose of ZDV to the mother are reported from 6 chronically catheterized baboons. The first order elimination half-life of ZDV from both the mother and fetus was approximately 1.2 hours. The area under the concentration-time curve for the fetus was 77% (r2 = 0.98; p < .001) that of the mother and the estimated peak drug levels in the fetus were 52% (r2 = 0.83; p < .01) those in the mother. The rapid transfer and short half-life of ZDV leads to a drug concentration-time profile that would not sustain levels in the fetus with dosing every 4 hours. After comparing these findings with existing data from pregnant and nonpregnant humans, it seems likely that current dose recommendations for ZDV in pregnancy would not maintain levels of the active intracellular metabolite of ZDV in all fetuses. This may explain in part the 8% failure rate of ZDV prophylaxis. The correlation between fetal and maternal plasma concentrations of ZDV would allow titration of dose based on maternal drug levels to achieve fetal levels within the therapeutic range.

Original languageEnglish (US)
Pages (from-to)433-440
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume19
Issue number5
DOIs
StatePublished - Dec 15 1998

Keywords

  • Baboon, maternal
  • Fetal exchange
  • Fetus
  • HIV
  • Pharmacokinetics
  • Placental transfer
  • Pregnancy
  • Zidovudine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

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