THE TRANSFER OF THE NUCLEOSIDE ANALOG GANCICLOVIR ACROSS THE PERFUSEDHUMAN PLACENTA

OBJECTIVE: 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. STUDY DESIGN: 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 tr ansfer mechanism of each agent. RESULTS: The clearance index for ganci clovir was 0.17 +/- 0.08 and 0.20 +/- 0.10 at 1 and 10 mu g/ml materna l concentrations. This was similar to the clearance index for acyclovi r, which was 0.17 +/- 0.06 and 0.18 +/- 0.12, respectively. The cleara nce index for ganciclovir was not significantly affected by the additi on of 5 mu mol/L dinitrobenzylthioinosine 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 con centrations of 1.0, 10.0, and 100 mu g/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. CONCLUSION: The antiviral age nts ganciclovir and acyclovir appear to cross the placenta by simple d iffusion, at least at therapeutic levels, and this transfer is not aff ected by the nucleoside transport inhibitor dinitrobenzylthioinosine.