Acyclovir transport by the human placenta.

Abstract

Genital Herpes simplex infection is noted increasingly in women of childbearing age and in neonates. Concern about transmission of herpes to the newborn has led to cesarean delivery of many pregnant women with a history of genital herpes. Severe herpes hepatitis has also been noted in pregnancy. Acyclovir is the drug of choice for this infectious organism. Because there are no data on the mechanism(s) of transport of this drug by the human placenta, this study addressed this issue. We used normal term human placentas. For study of overall placental transport of acyclovir, we used the single, isolated perfused cotyledon technique. For assessment of initial acyclovir uptake, we used microvesicles prepared from the maternal-facing syncytiotrophoblast. Overall transfer of acyclovir at therapeutic concentrations from maternal to fetal compartment was at a rate of about 30% that of a freely diffusible marker, antipyrine. The overall transport was not saturable, was not inhibited by 50-fold adenine concentration, and did not proceed against a concentration gradient. There was no placental metabolism of the drug. Fetal-to-maternal transfer of acyclovir was at a similar rate. In maternal-facing microvesicles net uptake of acyclovir was not saturable, but was temperature dependent and was inhibited by high concentrations of adenine and ganciclovir, but not by nucleosides (adenosine, cytidine, cytosine). These data are most consistent with a carrier-dependent, nucleobase-type uptake of the drug, but passive overall net transfer of acyclovir, dependent on its solubility characteristics.