TRANSFER OF DIDEOXYINOSINE ACROSS THE HUMAN ISOLATED PLACENTA

1 Dideoxyinosine (ddI) has recently been approved for the treatment of patients with HIV infection. As increasing numbers of such patients a re pregnant, we wished to define the rate and mechanism(s) of ddI tran sfer by the placenta to the foetus. Using isolated single perfused hum an term placental cotyledons, the drug was shown to cross the placenta from mother to foetus at a rate of 25% that of a freely diffusible ma rker, antipyrine, and at about half the rate of zidovudine (AZT). The transfer of ddI was similar in both directions (maternal to foetal and the reverse), equal to that of L-glucose, a passively transported sug ar, and was not inhibited by excess inosine or uric acid (structural a nalogues of ddI). ddI did not cross to the foetus against a concentrat ion gradient. The transport process appeared to be passive and it was not altered by AZT. 2 ddI was not metabolized in the Krebs Ringer buff er/albumin perfusate, and placental homogenates converted only 4% of d dI to hypoxanthine over the 4 h incubation. However, when maternal ter m or cord blood was incubated with ddI for 3 h, 50% of the drug was co nverted to hypoxanthine in maternal blood and to hypoxanthine and uric acid in cord blood. 3 Thus, ddI metabolism in maternal blood should d ecrease its net transfer to the foetus in vivo. In the foetal circulat ion, ddI will be further metabolized by erythrocytes to hypoxanthine a nd possibly to uric acid. Hence, the fraction of administered ddI deli vered to foetal tissues should be much lower than that of AZT.