TABLE 4.
IC50 values for mitragynine and kratom extracts against P450 and UGT activities using various test systems
| Enzyme | Substrate | Reaction | Enzyme System | Monitoring Method | Mitragynine (μM) | Extract (μg/ml) |
|---|---|---|---|---|---|---|
| CYP1A2 | phenacetin | O-deethylation | HLMs | LCMS | >45 | — |
| CEC | O-deethylation | recombinant | fluorometric | — | 39 | |
| CYP2C8 | amodiaquine | N-deethylation | HLMs | LCMS | 33.5 | — |
| CYP2C9 | diclofenac | 4’-hydroxylation | HLMs | LCMS | >45 | — |
| luciferin H | 9.7 | — | ||||
| diclofenac | 4’-hydroxylation | HLMs | LCMS | 39.7 | — | |
| CYP2C19 | S-mephenytoin | 4’-hydroxylation | HLMs | LCMS | 10.5 | — |
| CEC | O-deethylation | recombinant | fluorometric | — | 85 | |
| CYP2D6 | dextromethorphan | O-demethylation | HLMs | LCMS | 2.2 | — |
| AMMC | O-demethylation | recombinant | fluorometric | — | 0.64 | |
| luciferin ME-EGE | luminometric | 0.45 | — | |||
| luciferin ME-EGE | luminometric | — | 3.6 | |||
| dextromethorphan | O-demethylation | HLMs | LCMS | 0.67 | — | |
| CYP3A4/5 | Midazolam | 1’-hydroxylation | HLMs | LCMS | 11.4 | — |
| testosterone | 6β-hydroxylation | HLMs | LCMS | >45 | — | |
| BFC | O-debenzylation | recombinant | fluorometric | — | 0.78 | |
| midazolam | 1’-hydroxylation | recombinant | HPLC-UV | 17.31 | — | |
| testosterone | 6β-hydroxylation | recombinant | HPLC-UV | 3.98 | — | |
| luciferin-BE | luminometric | 41.32 | — | |||
| luciferin-BE | luminometric | — | 142.8 | |||
| midazolam | 1’-hydroxylation | HLMs | LCMS | 18.9 | — | |
| midazolam | 1’-hydroxylation | HIMs | LCMS | 21.9 | — | |
| UGT1A1 | 4-MU | glucuronidation | recombinant | HPLC-UV | >100 | — |
| UGT2B7 | zidovudine | glucuronidation | HLMs | HPLC-UV | 8.11 | — |
| 4-MU | glucuronidation | recombinant | HPLC-UV | >100 | — |
—, information not available.
AMMC, 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin; BFC, 7-benzyloxy-4-(trifluoromethyl)-coumarin; CEC, 3-cyano-7-ethoxycoumarin; HPLC-UV, high pressure liquid chromatography coupled with UV detector; luciferin-BE, luciferin 6’ benzyl ether; luciferin H, 6’deoxyluciferin; luciferin ME-EGE, ethylene glycol ester of luciferin 6’ methyl ether; 4-MU, 4-methylumbelliferone.