Ex Vivo Human Placental Transfer of Anti-Human Immunodeficiency Virus Compounds

Objective: The transfer of anti-human immunodeficiency virus (HIV) drugs has been studied in the ex vivo human placental model. There is a paucity of information on the placental transfer of these drugs because of ethical considerations and the expense involved in the use of the non-human primate model. Methods: The standardized ex vivo human placental model was used in these studies and the clearance index in relationship to antipyrine was used to determine the role of transfer of non-nucleosides, nucleosides, and a protease inhibitor. Several of the nucleosides and ritonavir were combined with zidovudine (AZT) to determine the effect of the combinations. Results: All non-nucleosides, nucleosides, and the protease inhibitor were found to cross the human placenta by simple diffusion, although at variable rates. Ritonavir did not diffuse as rapidly as the nucleosides, but some diffusion was noted at peak concentrations. Conclusions: Ex vivo perfusion studies agree with those determined in the non-human primate model and with data from existing clinical trials.