The transfer of anti-human immunodeficiency virus nucleoside compounds by the term human placenta

The purpose of this study was to compare the maternal-fetal placental transfer of 2',3'-dideoxyinosine and 2',3'-dideoxycytidine with that of 3'-azido-2', 3-dideoxythymidine (azidothymidine).

The perfusion system used carbon 14-labeled antipyrine as a reference compound to determine the clearance index of each compound. The inhibitor dipyridamole and the endogenous bases were used to determine if these anti-human immunodeficiency virus compounds crossed the placenta other than by simple diffusion.

The clearance index of azidothymidine was 0.29 +/- 0.04 at maternal concentrations of 1.0 to 10 micrograms/ml, and the clearance index of 2',3'-dideoxyinosine was 0.14 +/- 0.05, which was 48% of the clearance index of azidothymidine. The clearance index of 2',3'-dideoxyinosine was essentially identical to azidothymidine in the range from 1 to 10 micrograms/ml. The results of the closed-closed studies suggest that at therapeutic peak concentrations of 1 to 2 micrograms/ml of these compounds in the maternal circulation therapeutic levels will be reached in the fetal circulation.

These anti-human immunodeficiency virus inhibitors appear to cross the placenta rapidly by simple diffusion because (1) the transfer of the drugs to the fetal circulation was not saturable even at 100 micrograms/ml, (2) there was no change in clearance index with the addition of 300 mumol/L of thymidine, inosine, cytosine, or 30 mumol/L dipyridamole, and (3) there was no accumulation against the maternal fetal or fetal maternal concentration gradient.