The transfer of the nucleoside analog ganciclovir across the perfused human placenta.

Abstract

The purpose of this study was to compare the maternal-fetal placental transfer of the antiviral nucleoside analog ganciclovir to that of acyclovir and to investigate the mechanism of transport. The ex vivo human placental cotyledon model was used. Carbon 14-labeled antipyrine was used as the reference compound to determine the clearance index of both antiviral agents. Dinitrobenzylthioinosine was used as a nucleoside transport inhibitor to help determine the transfer mechanism of each agent. The clearance index for ganciclovir was 0.17 +/- 0.08 and 0.20 +/- 0.10 at 1 and 10 micrograms/ml maternal concentrations. This was similar to the clearance index for acyclovir, which was 0.17 +/- 0.06 and 0.18 +/- 0.12, respectively. The clearance index for ganciclovir was not significantly affected by the addition of 5 mumol/L dinitrobenzylthionosine to the perfusate (0.25 +/- 0.09 vs 0.20 +/- 0.05). The same was true for acyclovir (0.29 +/- 0.06 vs 0.22 +/- 0.07). When the closed system and maternal ganciclovir concentrations of 1.0, 10.0, and 100 micrograms/ml were used, the percent fetal levels compared with maternal levels at 1 hour were 17.2%, 19.2%, and 17.3%, respectively. For acyclovir the fetal levels were 15.6%, 9.1%, and 8.9% compared with maternal levels. The antiviral agents ganciclovir and acyclovir appear to cross the placenta by simple diffusion, at least at therapeutic levels, and this transfer is not affected by the nucleoside transport inhibitor dinitrobenzylthioinosine.