Cannabinoid fm valuesa in HLMs determined using selective P450 or UGT inhibitors and quantified by monitoring either THC/11-OH-THC depletion or formation of 11-OH-THC from THC
HLM incubations were conducted with observed concentrations of THC (500 nM) and 11-OH-THC (50 nM) after smoking marijuana. Inhibition of 11-OH-THC depletion by omeprazole and quinidine was negligible (data not shown). Data shown are the mean ± S.D. of three independent experiments with each experiment conducted in duplicate.
| Selective Inhibitor | Enzyme | THC Depletion | 11-OH-THC | |
|---|---|---|---|---|
| Formation | Depletion | |||
| Sulfaphenazole (10 μM) | CYP2C9 | 0.78 ± 0.03 | 0.90 ± 0.01 | 0.15 ± 0.04 |
| Itraconazole (2 μM) | CYP3A | 0.22 ± 0.05 | −0.11 ± 0.09 | 0.24 ± 0.06 |
| Omeprazole (30 μM) | CYP2C19 | 0.13 ± 0.11 | 0.54 ± 0.07 | Negligible |
| Quinidine (1 μM) | CYP2D6 | 0.15 ± 0.10 | 0.18 ± 0.20 | Negligible |
| Fluconazole (2 mM) | UGT2B7 | Negligible | N/A | 0.36 ± 0.05 |
| Niflumic acid (2.5 μM) | UGT1A9 | Negligible | N/A | 0.41 ± 0.04 |
N/A, not applicable.
↵a Data are not corrected for cross-inhibition of enzyme by the inhibitors.