GANCICLOVIR TRANSFER BY HUMAN PLACENTA AND ITS EFFECTS ON RAT FETAL CELLS

Cytomegalovirus is a common cause of intrauterine infection. Ganciclovir is an accepted therapeutic agent for this infection, but is proscribed in pregnancy, except when there is a life-threatening maternal infection, because of its known teratogenic and embryotoxic effects in experimental animals. There are no such data in humans and the human transplacental transfer of this drug has not been studied. This study defines the rate and mechanism of human-placental ganciclovir transport using maternal-facing syncytiotrophoblast vesicles and the perfused, isolated single-cotyledon system and determines further the effects of ganciclovir on fetal tissue, using cultured rat fetal hepatocytes. Ganciclovir was taken up by the maternal-facing placental membrane by a carrier-dependent, Na-independent system inhibited by adenine, guanine, and acyclovir, but not by cytosine and thymine or thymidine and uridine. By contrast, the overall transfer of the drug by the placenta was passive and without drug metabolism. Therefore, the drug is concentrated initially at the maternal placental surface and then crosses passively into the fetal compartment, with the latter process being rate-limiting. There was little or no toxic effect of high concentrations of ganciclovir on cultured fetal-rat hepatocytes.