TABLE 3.
Intrinsic clearance (microliters per minute per milligram) measured for known and new UGT2B10 substrates using UDPGA and NADPH as a cofactor and fm(gluc) and fm(UGT2B10)
| UGT2B10 Substrates | Drug | Clint (UGT) (µl/min per milligram) | Clint (CYP) (µl/min per milligram) | Total Clint (µl/min per milligram) | fm(gluc) | fm(UGT2B10) |
|---|---|---|---|---|---|---|
| Known selective UGT2B10 substrates | Amitriptyline | 2.5 ± 0.6 | 5.0 ± 0.7 | 7.5 ± 0.9 | 0.33 | 0.32 |
| Dexmedetomidine | 17 ± 1 | 4.4 ± 0.2 | 21 ± 1 | 0.79 | 0.79 | |
| Cyclizine | 16 ± 2 | 6.6 ± 2.3 | 23 ± 3 | 0.71 | 0.70 | |
| Chlorcyclizine | 17 ± 5 | 5.2 ± 0.3 | 22 ± 5 | 0.77 | 0.76 | |
| RO5263397 | 35 ± 3 | <2.3 | <37.3 | >0.94 | >0.93 | |
| New selective UGT2B10 substrates | Cyclobenzaprine | 2.1 ± 0.7 | 8.2 ± 1.1 | 10 ± 1 | 0.20 | 0.20 |
| Dothiepin | 3.7 ± 0.6 | 5.0 ± 1.2 | 8.7 ± 1 | 0.43 | 0.41 | |
| Cidoxepin | 6.0 ± 0.3 | 6.9 ± 1.1 | 13 ± 1 | 0.47 | 0.46 | |
| Cyproheptadine | 23 ± 3 | 13 ± 1 | 36 ± 3 | 0.64 | 0.63 | |
| Azatadine | 14 ± 1 | 6.6 ± 0.9 | 21 ± 1 | 0.68 | 0.68 | |
| Bifonazole | 11 ± 1 | 67 ± 7 | 78 ± 7 | 0.14 | 0.14 | |
| Asenapine | 27 ± 2 | 27 ± 1 | 54 ± 2 | 0.50 | 0.49 |