Mechanism and rate of placental transfer of zalcitabine (2',3'-dideoxycytidine) in Macaca nemestrina.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Mechanism and rate of placental transfer of zalcitabine (2',3'-dideoxycytidine) in Macaca nemestrina.

Am J Obstet Gynecol. 1996 Mar;174(3):856-63. Unique Identifier : AIDSLINE MED/96203540
Tuntland T; Nosbisch C; Baughman WL; Massarella J; Unadkat JD; Department of Pharamceutics, School of Pharmacy, University of; Washington, Seattle 98195-7610, USA.

Abstract: OBJECTIVE: Our purpose was to determine whether the ant-human immunodeficiency virus drug zalcitabine (2',3'-dideoxycytidine) is actively transferred across the placenta in the near-term Macaca nemestrina. STUDY DESIGN: Constant rate infusions of zalcitabine (1.31 microg/min/kg) and antipyrine (66.7 microg/min/kg) were administered to the dam through the femoral vein (n = 4) or to the fetus through the carotid artery (n = 3) in a randomized cross-over design. Zalcitabine was also administred at a 10-fold higher infusion rate to the dam (n = 3). The effect of zidovudine on the transplacental transfer of zalcitabine was studied by coinfusing the two drugs to the dam (n = 2). Samples from maternal plasma, fetal plasma, and amniotic fluid were collected at regular intervals during the 30-hour infusions. RESULTS: The maternal-fetal transfer clearance of zalcitabine (0.41 +/- 0.16 ml/min/kg) was not significantly different from the fetal-maternal transfer clearance of the drug (0.66 +/ 0.30 ml/min/kg). Moreover, the steady-state fetal-maternal plasma concentration ratios of zalcitabine after the low 0.58 +/- 0.06) and high (0.66 +/- 0.10) infusion rates to the dam were similar. This ratio was not substantially changed (0.69) when zalcitabine was coadministered with zidovudine. The placental transfer rate of zalcitabine was 11% (+/-4%) that of antipyrine. CONCLUSION: The placental transfer of zalcitabine is passive and unaffected by simultaneous administration of zidovudine. In Macaca nemestrina the average fetal exposure to zalcitabine is approximately 60% of the maternal exposure.

Keywords: Amniotic Fluid/METABOLISM Animal Anti-Inflammatory Agents, Non-Steroidal/PHARMACOLOGY Antipyrine/PHARMACOKINETICS Antiviral Agents/BLOOD/*PHARMACOKINETICS Cattle Cross-Over Studies Drug Interactions Female Fetal Blood/METABOLISM Macaca nemestrina Placenta/*METABOLISM Pregnancy Random Allocation Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Zalcitabine/BLOOD/*PHARMACOKINETICS Zidovudine/PHARMACOKINETICS JOURNAL ARTICLE
960930
M9690862

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