Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2484997 | Journal of Pharmaceutical Sciences | 2013 | 12 Pages |
Abstract
Ritonavir (RTV) is not only an inhibitor but also an immunoreactive inducer of both P-glycoprotein (Pgp) and cytochrome P450 (CYP) 3A in terms of its chronic use. The aim of present study was to test the hypothesis that the power balance between inhibition effects of RTV and induced activities of Pgp and CYP3A depends on the time after last RTV treatment (TimeR) in the chronic use of RTV; rhodamine 123 (Rho) and midazolam (MDZ) were administered at predetermined TimeR to rats pretreated with RTV for 7 days. After oral administration of Rho and MDZ to rats pretreated with RTV for 7 days, the areas under the plasma concentration-time curve of Rho and MDZ were significantly altered depending on TimeR: 1.27-, 0.79-, 0.95-, and 0.11-fold increases over that of the control for Rho at TimeRÂ =Â 0, 3, 9, and 24Â h and 3.12-, 1.50-, 1.27-, and 0.17-fold increases over that of the control for MDZ at TimeRÂ =Â 0, 3, 9, and 24Â h, respectively. These results revealed the presence of the time-dependent interaction of RTV with concomitant drugs in chronic use and should be taken into account in therapeutic strategies for HIV infection.
Keywords
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Authors
Keizo Fukushima, Shinji Kobuchi, Kazunori Mizuhara, Hiroaki Aoyama, Kanji Takada, Nobuyuki Sugioka,