Kinetic parameters for methadone N-demethylation
| Parameter | Single Enantiomer Metabolism | Racemate Metabolism | ||||||
|---|---|---|---|---|---|---|---|---|
| CYP2B6.1 | CYP2B6.6 | CYP2B6.1 | CYP2B6.6 | |||||
| R-EDDP Formation | S-EDDP Formation | R-EDDP Formation | S-EDDP Formation | R-EDDP Formation | S-EDDP Formation | R-EDDP Formation | S-EDDP Formation | |
| Ks (µM) | 75 ± 18 | 25 ± 5 | 97 ± 7 | 40 ± 7 | 40 ± 20 | 13 ± 3 | 57 ± 6 | 20 ± 3 |
| Vmax (nmol/nmol P450/min) | 20.8 ± 0.6 | 14.6 ± 1.0 | 5.7 ± 0.3 | 3.5 ± 0.3 | 18.9 ± 7.4 | 8.7 ± 0.2 | 4.7 ± 0.6 | 5.1 ± 0.2 |
| Clint (ml/min/nmol) | 0.3 ± 0.1 | 0.6 ± 0.1 | 0.06 ± 0.01 | 0.09 ± 0.02 | 0.5 ± 0.3 | 0.7 ± 0.2 | 0.08 ± 0.01 | 0.3 ± 0.1 |
Clint, intrinsic clearance; EDDP, 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine; Ks, equilibrium dissociation constant for the enzyme-substrate complex; P450, cytochrome P450.