TheEx VivoHuman Placental Transfer of theAnti-HIV Nucleoside Inhibitor Abacavir and theProtease Inhibitor Amprenavir

[摘要] Objective:The transfer of abacavir, a new nucleoside inhibitor, and amprenavir, a new proteaseinhibitor, used for the treatment of human immunodeficiency virus, has been studied in theex vivohuman placental model.Methods:Theex vivohuman placental model used C14antipyrine to determine the transportfraction 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 highpressure liquid chromatography.Results:The clearance index of abacavir was 0.47 ± 0.19 and 0.50 ± 0.07 at peak and troughconcentrations, respectively. The clearance index of amprenavir was 0.38 ± 0.09 and 0.14 ± 0.08 atpeak and trough concentrations, respectively. There was no unusual accumulation of either drug inthe media or tissue when the perfusion system was closed.Conclusion:Abacavir is the first nueleoside compound studied in the perfusion system with a highclearance index. The transfer of the protease inhibitor amprenavir had a clearance index 2.75 timesgreater 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. Asimilar result was found with ritonavir.

[学科分类] 妇产科学