Table 3.
Kinetic parameters derived for NBIF-related glucuronides (G1 and G2) by HLM, HIM, expressed UGT enzymes, MkLM, RLM, MLM, DLM and RaLM (mean ± SD). All experiments were performed in triplicate.
| Enzyme | Meta. | Vmax (pmol/min/mg) | Km (μM) | Ki (μM) | CLint (μL/min/mg) | Model |
|---|---|---|---|---|---|---|
| HLM | G1 | 1788.0 ± 203.6 | 6.58 ± 1.25 | 48.45 ± 13.86 | 271.90 ± 60.39 | SI |
| G2 | 919.1 ± 20.23 | 1.41 ± 0.13 | N.A. | 651.38 ± 60.31 | MM | |
| HIM | G1 | 409.3 ± 18.9 | 6.83 ± 0.91 | N.A. | 59.96 ± 8.42 | MM |
| G2 | 8655.0 ± 1021.0 | 9.12 ± 1.64 | 33.32 ± 7.95 | 949.01 ± 203.75 | SI | |
| UGT1A1 | G1 | 912.4 ± 49.36 | 3.64 ± 0.48 | 291.1 ± 100.1 | 250.87 ± 35.80 | SI |
| G2 | 48.33 ± 1.59 | 1.03 ± 0.11 | 401.2 ± 135.7 | 47.01 ± 5.35 | SI | |
| UGT1A7 | G1 | 11.93 ± 0.55 | 0.41 ± 0.06 | 61.82 ± 13.5 | 28.87 ± 4.57 | SI |
| G2 | 135.3 ± 4.36 | 0.31 ± 0.04 | 154.5 ± 44.85 | 438.15 ± 56.41 | SI | |
| UGT1A8 | G1 | 419.1 ± 18.69 | 4.52 ± 0.54 | N.A. | 92.68 ± 11.73 | MM |
| G2 | 147.0 ± 6.84 | 4.0 ± 0.51 | N.A. | 36.75 ± 5.00 | MM | |
| UGT1A9 | G1 | 70.01 ± 1.37 | 1.77 ± 0.14 | N.A. | 39.49 ± 3.11 | MM |
| G2 | 805.9 ± 17.46 | 0.75 ± 0.07 | N.A. | 1073.25 ± 108.93 | MM | |
| UGT2B4 | G2 | + | + | + | + | |
| MkLM | G1 | 4129.0 ± 182.8 | 11.39 ± 1.25 | N.A. | 362.51 ± 42.87 | MM |
| G2 | 7072.0 ± 228.4 | 5.62 ± 0.55 | N.A. | 1257.92 ± 129.47 | MM | |
| RLM | G1 | 2490.0 ± 249.5 | 6.40 ± 1.01 | 24.73 ± 4.75 | 388.88 ± 72.83 | SI |
| G2 | 826.6 ± 99.48 | 2.95 ± 0.57 | 9.09 ± 1.82 | 280.11 ± 63.39 | SI | |
| MLM | G1 | 3589.0 ± 432.9 | 7.41 ± 1.43 | 38.19 ± 10.18 | 484.67 ± 110.41 | SI |
| G2 | 3878.0 ± 563.1 | 8.84 ± 1.96 | 31.68 ± 9.16 | 438.64 ± 116.08 | SI | |
| DLM | G1 | 1807.0 ± 48.14 | 9.31 ± 0.65 | N.A. | 194.09 ± 14.55 | MM |
| G2 | 3363.0 ± 85.47 | 3.48 ± 0.30 | N.A. | 965.27 ± 86.90 | MM | |
| RaLM | G1 | 3006.0 ± 103.8 | 4.82 ± 0.43 | N.A. | 623.26 ± 60.06 | MM |
| G2 | 3411.0 ± 155.5 | 4.13 ± 0.51 | N.A. | 826.61 ± 109.47 | MM |
Note: Meta., metabolites; N.A., not available; +, under the limit of quantification; HLM, human liver microsomes; HIM, human intestine microsomes; MkLM, monkeys liver microsomes; RLM, rats liver microsomes; DLM, dogs liver microsomes; MLM, mice liver microsomes; RaLM, rabbits liver microsomes; SI, substrate inhibition model; MM, Michaelis-Menten model.