Individual enzyme kinetic parameters for fluvastatin metabolism
| Recombinant Enzymes | Human Liver Microsomes (Extrapolated Contribution of Isoenzyme) | |||
|---|---|---|---|---|
| Enzyme/Metabolite | Km | Vmax nmol/h/nmol CYP (nmol/h/mg protein) | Vmax nmol/h/nmol CYP (nmol/h/mg protein) | Clmt ml/h/nmol CYP (ml/h/mg protein) |
| μM | ||||
| CYP 3A4/5-OH2-a | 7.1 | 120 (29) | 14 (5.7) | 1.9 (0.8) |
| CYP 2C9R144/6-OH | 0.9 | 4.7 (2.4) | 1.1 (0.5) | 1.2 (0.5) |
| CYP 2C9R144/5-OH | 1.0 | 2.3 (1.2) | 0.5 (0.2) | 0.5 (0.2) |
| CYP 2C9R144/N-deisopropyl | 1.8 | 2.3 (1.2) | 0.4 (0.2) | 0.2 (0.1) |
| CYP 2C9C144/6-OH | 1.2 | 3.6 (1.7) | 1.1 (0.5) | 0.9 (0.4) |
| CYP 2C9C144/5-OH | 1.0 | 1.5 (0.7) | 0.5 (0.2) | 0.5 (0.2) |
| CYP 2C9C144/N-deisopropyl | 1.3 | 1.6 (0.8) | 0.5 (0.2) | 0.4 (0.2) |
| CYP 2C8/5-OH | 2.8 | 7.9 (2.9) | 0.2 (0.3) | 0.1 (0.1) |
Michaelis-Menten parameters were determined from recombinant baculovirus/insect cell microsomes expressing active, human CYP2C8, CYP2C9R144, CYP2C9C144, or CYP3A4. Maximal velocities were extrapolated to human liver microsomes using the ratio of reference activities in a panel of human liver microsomes compared recombinant with enzymes: CYP3A, testosterone; CYP2C9, diclofenac; CYP2C8 6α-hydroxy-paclitaxel (Crespi and Penman, 1997).
↵2-a mean of two experiments