THE EX-VIVO TRANSFER OF THE ANTI-HIV NUCLEOSIDE COMPOUND D4T IN THE HUMAN PLACENTA

The purpose of this study was to determine the ex vivo maternal-fetal placental transfer of 2',3'-didehydro-3'-deoxythymidine (d4T) and to c ompare it to the perfusion characteristics of 3'-azido-2',3-dideoxythy midine (AZT). This study used the single cotyledon perfusion system an d antipyrine to determine the clearance index of this thymidine-contai ning anti-human immunodeficiency virus (HIV) compound. The endogenous base thymidine and the inhibitor dipyridamole were used to determine i f this anti-HIV compound crossed the placenta by simple diffusion. The clearance index of d4T was 0.24 +/- 0.07 at 1.0 mu g/ml and 0.235 +/- 0.045 at 10.0 mu g/ml. These data suggest that the clearance index of d4T is 77-81% of AZT. The presence of high concentrations of dipyrida mole and endogenous thymidine did not alter the clearance of d4T. In s tudies in which both the maternal and fetal circulations were closed, the accumulation in the fetal circulation was linear when the maternal concentration was in the range of 1-100 mu g/ml. These data suggest t hat d4T crosses the human placenta by simple diffusion, and has simila r perfusion characteristics to that of AZT.