Transfer and metabolism of dideoxyinosine by the perfused human placenta

Dideoxyinosine (DDI) has been recently approved for the treatment of AIDS. In anticipation of its use in HIV-infected women during pregnancy, the transfer and metabolism of DDI by the perfused human placenta have been investigated. Transfer characteristics are those of simple diffusion: clearance is the same as that for L-glucose (transfer index of 0.98 +/- 0.09), it is equivalent in both directions across the placenta, and the transfer rate is proportional to the transplacental gradient over a very broad range (1 to 500 microM). Because of extensive placental metabolism, only about one-half of the cleared DDI (51 +/- 21%) is transferred intact to the fetal circulation. No dideoxyadenine triphosphate, the antiviral product of DDI, could be detected in the placenta following perfusion. Comparison of the pharmacological information on DDI and zidovudine (ZDV) indicates that treatment of HIV-infected women during pregnancy with DDI will expose the fetus to much less drug than if ZDV were used. DDI may therefore be less effective than ZDV in the treatment of the infected fetus. However, the uninfected fetus of an HIV-infected woman will gain by reduced exposure to a drug that is known to be toxic.