The ex vivo human placental transfer of the anti-HIV nucleoside inhibitor abacavir and the protease inhibitor amprenavir.
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.


CONCLUSIONS
Abacavir is the first nucleoside 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.
Bawdon
R E
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Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas 75235-9032, USA.
D002219:Carbamates; D015224:Dideoxynucleosides / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D013449:Sulfonamides / Q000493:pharmacokinetics* / Q000494:pharmacology; D000099227:Abacavir