Ll. Von Moltke et al., Potent mechanism-based inhibition of human CYP3A in vitro by amprenavir and ritonavir: comparison with ketoconazole, EUR J CL PH, 56(3), 2000, pp. 259-261
Objective: Biotransformation of triazolam to its a-hydroxy and 4-hydroxy me
tabolites 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 vira
l protease inhibitors ritonavir (IC50 = 0.14 mu M) and amprenavir (IC50 = 2
.5-2.9 mu M), and by the azole derivative ketoconazole (IC50 = 0.07 mu M) P
re-incubation of microsomes with ritonavir or amprenavir increased inhibito
ry potency (IC50 reduced to 0.07 mu M and 1.4 mu M, respectively). This was
not the case with ketoconazole.
Conclusions: Thus, ritonavir and amprenavir are highly potent mechanism-bas
ed inhibitors of human CYP3A isoforms.