Inhibitor | Atorvastatin | Atorvastatin Lactone | ||
---|---|---|---|---|
para-Hydroxy | ortho-Hydroxy | para-Hydroxy | ortho-Hydroxy | |
Fluconazole | 9.1 ± 2.8 | 7.5 ± 3.6 | 12.8 ± 3.7 | 18.5 ± 2.6 |
Saquinavir | 0.6 ± 0.4 | 0.6 ± 0.5 | 0.5 ± 0.4 | 0.4 ± 0.2 |
Itraconazole | 0.05 ± 0.03 | 0.04 ± 0.01 | 0.03 ± 0.01 | 0.03 ± 0.01 |
Atorvastatin | 90.0 ± 28.5 | >90 | ||
Atorvastatin lactone | 0.9 ± 0.4 | 0.9 ± 0.3 |
Apparent inhibition constants (Ki) are given as mean ± S.D. (n = 4 different preparations of human liver microsomes). For the inhibition studies, atorvastatin and atorvastatin lactone concentrations close to theirKm (Table 1) were chosen. ApparentKi values were estimated based on half-maximal inhibition concentrations (IC50), which were determined separately for para- and ortho-hydroxy metabolite formation, and the apparent Km values shown in Table1 using the Cheng-Prusoff equation (Cheng and Prusoff, 1973).