The maternal-fetal transfer of bisheteroypiperazine (U-87201-E) in the ex vivo human placenta

OBJECTIVE: The purpose of this study was to elucidate the maternal-fetal transfer of bisheteroypiperazine (U-87201-E), a nonnucleoside reverse transcriptasae inhibitor of human immunodeficiency virus-1. STUDY DESIGN: Placentas from normal term deliveries were used in this study to determine the maternal-fetal transfer of bisheteroypiperazine. The studies were conducted at several concentrations with the circulation either open-open or closed-closed. RESULTS: In this study we determined that the clearance index of bisheteroypiperazine was 0.72 ± 0.17 at maternal concentrations of 1.0 and 20.0 μg/ml. This is at least twice the clearance index of 3′-azido-2′, 3′-dideoxythymidine and more than five times greater than that of 2′,3′-dideoxyinosine. CONCLUSIONS: Bisheteroypiperazine crosses the maternal-fetal membranes by simple diffusion, in some instances almost equivalent to the refernece compound antipyrine. Placental tissue concentrations were equivalent at all maternal concentrations, suggesting saturation. This high rate of maternal-fetal transfer suggests that it may be an effective prophylactic drug for fetuses of human immunodeficiency virus-infected mothers.