Hepatic glucuronidation activities using 10 UGT probe substrates in pooled HLMs and in the presence of increasing UDPGA concentrations (1, 2.5, 3.75, 5, 8, 12, 16, and 25 mM)
Values are presented as the mean ± S.D. unless otherwise mentioned.
| UGT Substrate Concentration (5 µM) | Km | Maximal Reaction Rate | S50 | Hill Coefficient | Ki | Maximal Activity at 5 mM UDPGA | Model |
|---|---|---|---|---|---|---|---|
| mM | mM | mM | % | ||||
| β-Estradiol | 1.77 ± 0.14 | 0.64 ± 0.01 | N/A | N/A | N/A | 73 | MM |
| Chenodeoxycholic acid | 4.79 ± 0.80 | 0.27 ± 0.01 | 2.29 ± 0.12 | 1.89 ± 0.18 | N/A | 80 | SMM |
| Trifluoperazine | 9.13 ± 0.99 | 0.34 ± 0.02 | 5.59 ± 0.56 | 1.29 ± 0.11 | N/A | 47 | SMM |
| 5-Hydroxytryptophol | 2.79 ± 1.74 | 1.02 ± 0.40 | N/A | N/A | 3.69 ± 2.02 | 84c | SI |
| Propofol | 0.80 ± 0.17 | 0.09 ± 0.00 | N/A | N/A | N/A | 76 | MM |
| Gemfibrozil | 0.04 ± 0.10 | 0.40 ± 0.02 | N/A | N/A | 113.7 ± 61.8 | 89c | SI |
| Zidovudinea | 2.47 ± 0.33 | 0.29 ± 0.01 | N/A | N/A | N/A | 65 | MM |
| Amitriptyline | 3.07 ± 0.19 | 1.19 ± 0.07 | 4.47 ± 0.83 | 0.75 ± 0.07 | N/A | 52 | SMM |
| Oxazepamb | 1.02 ± 0.12 | 0.07 ± 0.00 | 1.04 ± 0.18 | 0.68 ± 0.14 | N/A | 75 | SMM |
| Testosterone | 1.63 ± 0.20 | 1.59 ± 0.03 | 1.28 ± 0.07 | 1.94 ± 0.21 | N/A | 96 | SMM |
Ki, substrate inhibition constant; Km, UDPGA affinity constant; MM, hyperbolic Michaelis–Menten model; N/A, not available; S50, UDPGA concentration at which half of maximal activity is reached; SI, substrate inhibition model; SMM, sigmoid Michaelis–Menten model.
↵a Incubation of 100 µM zidovudine.
↵b Incubation of racemic oxazepam.
↵c Maximal activity reached at 2.5 mM UDPGA.