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Potent mechanism-based inhibition of human CYP3A in vitro by amprenavir and ritonavir: comparison with ketoconazole.
- Source :
- European Journal of Clinical Pharmacology; Jun2000, Vol. 56 Issue 3, p259-261, 3p
- Publication Year :
- 2000
-
Abstract
- Objective: Biotransformation of triazolam to its α-hydroxy and 4-hydroxy metabolites by human liver microsomes in vitro was used as an index of human cytochrome P<subscript>450</subscript> 3A (CYP3A) activity. Results: The reaction was strongly inhibited by co-incubation with the viral protease inhibitors ritonavir (IC<subscript>50</subscript>=0.14 μM) and amprenavir (IC<subscript>50</subscript>=2.5–2.9 μM), and by the azole derivative ketoconazole (IC<subscript>50</subscript> = 0.07 μM). Pre-incubation of microsomes with ritonavir or amprenavir increased inhibitory potency (IC<subscript>50</subscript> reduced to 0.07 μM and 1.4 μM, respectively). This was not the case with ketoconazole. Conclusions: Thus, ritonavir and amprenavir are highly potent mechanism-based inhibitors of human CYP3A isoforms. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00316970
- Volume :
- 56
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- European Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15732888
- Full Text :
- https://doi.org/10.1007/s002280000125