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

Abstract

OBJECTIVE: Our purpose was to determine whether the anti-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 μg/min/kg) and antipyrine (66.7 μg/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 administered 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. (A M J O BSTET G YNECOL 1996;174:856-63.)