Open AccessThe Ex Vivo human placental transfer of the anti‐HIV nucleoside inhibitor abacavir and the protease inhibitor amprenavir
Author(s) -
Bawdon R.E.
Publication year - 1998
Publication title -
infectious diseases in obstetrics and gynecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.656
H-Index - 48
eISSN - 1098-0997
pISSN - 1064-7449
DOI - 10.1002/(sici)1098-0997(1998)6:6<244::aid-idog4>3.0.co;2-b
Subject(s) - amprenavir , ritonavir , abacavir , trough concentration , pharmacology , chemistry , pharmacokinetics , in vivo , ex vivo , nucleoside , protease inhibitor (pharmacology) , reverse transcriptase inhibitor , protease , virology , medicine , biology , biochemistry , viral load , enzyme , hiv 1 protease , virus , reverse transcriptase , in vitro , antiretroviral therapy , microbiology and biotechnology , rna , gene
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 C 14 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 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. Infect. Dis. Obstet. Gynecol. 6:244–246, 1998. © 1999 Wiley‐Liss, Inc.