Microsomes | Metabolite Formation |
---|---|
Human liver microsomes, Mean ± S.E. for n = 4 livers | |
K _{m} (μM) | 14.4 ± 2.0 |
K _{s} (μM) | 164.7 ± 15.1 |
Expressed human cytochromes, Fitted function values ± asymptotic S.E. | |
CYP3A | |
V _{max} | 1.9 ± 0.2 |
K _{m} (μM) | 23.1 ± 7.5 |
K _{s} (μM) | 918.7 ± 411.9 |
V _{max}/K _{m} ratio (% of total) | 79.1% |
CYP2C9 | |
V _{max} | 0.2 ± 0.006 |
K _{m} (μM) | 9.6 ± 1.2 |
V _{max}/K _{m} ratio (% of total) | 20.0% |
CYP2C19 | |
V _{max} | 0.02 ± 0.003 |
K _{m} (μM) | 23.1 ± 13.0 |
V _{max}/K _{m} ratio (% of total) | 0.83% |
CYP2D6^{1-150} |
Because standards were not available, absolute units were not assigned to V_{max} values. However, since the role of each cytochrome has been determined relative to the others,V_{max} values for microsomes containing cDNA-expressed enzymes are expressed in relative units (chromatographic peak height ratios) and their V_{max}/K_{m} values have been normalized for the relative hepatic abundance of each cytochrome.
↵1-150 , Data points could not be fit to Michaelis-Menten kinetics. However, CYP2D6 does not appear to account for greater than 2% of sildenafil biotransformation.