Abstract
Objective: The transfer of abacavir, a new nucleoside inhibitor, and amprenavir, a new protease inhibitor, used for the treatment of human immunodeficiency virus, has been studied in the ex vivo human placental model.Methods: The ex vivo human placental model used C14 antipyrine to determine the transport fraction and clearance index of these compounds at both the peak and trough serum concentrations. The clearance index accumulation and tissue concentrations were determined for each drug by high pressure liquid chromatography.Results: The clearance index of abacavir was 0.47 ± 0.19 and 0.50 ± 0.07 at peak and trough concentrations, respectively. The clearance index of amprenavir was 0.38 ± 0.09 and 0.14 ± 0.08 at peak and trough concentrations, respectively. There was no unusual accumulation of either drug in the media or tissue when the perfusion system was closed.Conclusion: Abacavir is the first nueleoside compound studied in the perfusion system with a high clearance index. The transfer of the protease inhibitor amprenavir had a clearance index 2.75 times greater than the clearance index of ritonavir at peak concentration determined in a previous study. At trough concentration the clearance index was much less than at the peak concentration. A similar result was found with ritonavir.
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