title: The transfer of the nucleoside analog ganciclovir across the perfused human placenta.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9032.
authors.forename: L C
authors.initials: LC
authors.lastname: Gilstrap
authors.forename: R E
authors.initials: RE
authors.lastname: Bawdon
authors.forename: S W
authors.initials: SW
authors.lastname: Roberts
authors.forename: S
authors.initials: S
authors.lastname: Sobhi
mesh_terms: D000212:Acyclovir / Q000493:pharmacokinetics; D001692:Biological Transport; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D005260:Female; D015774:Ganciclovir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D015774:Ganciclovir; D000212:Acyclovir