TABLE 3.
Kinetic parameters estimate and CV% using the P450 and UGT kinetic models
The P450 and UGT kinetic models were fitted to data from three to four independent experiments (see Materials and Methods and Fig. 3). Kinetic parameters shown in Table 2 were used as initial estimates. Data shown are parameter estimate and the confidence in these estimates (CV%). Km,u and CLint parameter estimates and CV% were corrected for incubation binding using fuinc.
| Pathway | Enzyme(s) | Vmax | Km | Km,u | CLint |
|---|---|---|---|---|---|
| pmol/min per milligram | μM | nM | ml/min per milligram | ||
| THC depletiona | P450s | — | — | — | 235.6 (48%) |
| 11-OH-THC formation | CYP2C9 | 624 (2%) | 0.07 (4%) | 3 (36%) | 214.4 (34%) |
| Unknown THC metabolite formationb | CYP2D6 | 4905 (17%) | 5.48 (20%) | 231 (44%) | 21.3 (34%) |
| 11-OH-THC depletiona | P450s/UGTs | — | — | — | 12.3 (26%) |
| COOH-THC formation | CYP2C9 | 5 (2%) | 0.50 (4%) | 32 (44%) | 0.15 (34%) |
| Unknown 11-OH-THC metabolite formationb | CYP2C9 | 54 (6%) | 0.50 (4%) | 32 (44%) | 1.7 (34%) |
| Unknown 11-OH-THC metabolite formationb | CYP3A | 1826 (6%) | 12.8 (8%) | 824 (59%) | 2.2 (34%) |
| Unknown 11-OH-THC metabolite formationb | UGT2B7/1A9 | 343 (4%) | 0.64 (4%) | 39 (44%) | 8.8 (44%) |
a
Depletion of THC or 11-OH-THC signifies total (aggregated) depletion and is reported as the sum of the CLint values of the various enzymatic pathways.
b
Metabolite formed not measured.