Placental Transport of Zidovudine in the Rhesus Monkey

Louis E. Ridgway, Thomas S. King, George I. Henderson, Steven Schenker, Robert S. Schenken

Research output: Contribution to journalArticle

Abstract

Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and fetal circulations of the rhesus monkey. Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at 120-130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood samples were collected every 20 min for the first 2 h and then every hour for the next 4 h. Maternal and fetal concentrations of ZDV and ZDVG were determined using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results: In monkeys who received ZDV, the terminal half-life (T1/2) for ZDV was 37 ± 15 and 33 ± 13 min in the maternal and fetal compartments, respectively. The apparent T1/2 for maternal ZDVG was 124 ± 44 and 142 ± 50 min in the maternal and fetal compartments, respectively. Peak levels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The mean fetal/maternal concentration ratios for ZDV and ZDVG ranged from 0.20 ± 0.20 at 20 min to a maximum of 0.74 ± 1.0 at 120 min and from 0.28 ± 0.08 at 20 min to 1.4 ± 1.3 at 180 min, respectively. In monkeys who received ZDVG, the T1/2 for ZDVG in the maternal and fetal compartments was 47 ± 26 and 119 ± 164 min, respectively. ZDVG reached its peak in the fetal compartment at 60 min post-injection. The fetal/maternal ratio ranged from 0.08 ±0.11 at 20 min to 4.2 ± 4.2 at 180 min post-injection. Conclusions: These data demonstrate that 1) ZDV and ZDVG rapidly cross the placenta to the fetal compartment, 2) ZDV crosses more rapidly than ZDVG, and 3) some metabolism of ZDV to ZDVG occurs in the fetal compartment.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalInfectious diseases in obstetrics and gynecology
Volume1
Issue number3
DOIs
StatePublished - 1993

Keywords

  • Macacca mulatta
  • Zidovudine
  • pharmacokinetics
  • zidovudine-glucuronide

ASJC Scopus subject areas

  • Dermatology
  • Obstetrics and Gynecology
  • Infectious Diseases

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