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


METHODS
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.


CONCLUSIONS
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.
Tuntland
T
T
Department of Pharamceutics, School of Pharmacy, University of Washington, Seattle 98195-7610, USA.
Nosbisch
C
C
Baughman
W L
WL
Massarella
J
J
Unadkat
J D
JD
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000983:Antipyrine / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D002417:Cattle; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D008254:Macaca nemestrina; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011897:Random Allocation; D016047:Zalcitabine / Q000097:blood / Q000493:pharmacokinetics*; D015215:Zidovudine / Q000493:pharmacokinetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000998:Antiviral Agents; D015215:Zidovudine; D016047:Zalcitabine; D000983:Antipyrine