Potent mechanism-based inhibition of human CYP3A in vitro by amprenavir and ritonavir: comparison with ketoconazole
| ISSN: |
1432-1041
|
|---|---|
| Keywords: |
Key words Human CYP3A ; Amprenavir ; Ritonavir
|
| Source: |
Springer Online Journal Archives 1860-2000
|
| Topics: |
Chemistry and Pharmacology
Medicine
|
| Notes: |
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 450 3A (CYP3A) activity. Results: The reaction was strongly inhibited by co-incubation with the viral protease inhibitors ritonavir (IC50=0.14 μM) and amprenavir (IC50=2.5–2.9 μM), and by the azole derivative ketoconazole (IC50 = 0.07 μM). Pre-incubation of microsomes with ritonavir or amprenavir increased inhibitory potency (IC50 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.
|
| Type of Medium: |
Electronic Resource
|
| URL: |