Table 1.
Kinetic parameters of propofol-O-glucuronidation, fraxetin-8-O-glucuronidation (G1), and fraxetin-7-O-glucuronidation (G2) by the UGT1A9 enzyme and by the HeLa1A9 cell lysate supplemented with uridine diphosphate glucuronic acid (UDPGA).
| Substrate | Metabolite | Enzyme | Vmax (pmol/min/mg) | Km (μM) | CLint [μL/(min.mg)] | Model |
|---|---|---|---|---|---|---|
| propofol | propofol-G | UGT1A9 | 61 ± 2 | 53 ± 6 | 1.2 ± 0.1 | MM |
| propofol | propofol-G | HeLa1A9 cell lysate | 3.2 ± 0.2 (aaa) | 59 ± 13 | 0.10 ± 0.01 (aaa) | MM |
| fraxetin | G1 | UGT1A9 | 2920 ± 160 | 16 ± 2 | 180 ± 28 | MM |
| fraxetin | G2 | UGT1A9 | 1440 ± 61 | 10 ± 1 | 150 ± 20 | MM |
| fraxetin | G1 | HeLa1A9 cell lysate | 110 ± 5 (bbb) | 13 ± 2 | 9 ± 1 (bbb) | MM |
| fraxetin | G2 | HeLa1A9 cell lysate | 42 ± 2 (ccc) | 8 ± 1 | 5 ± 1 (ccc) | MM |
Data are presented as mean ± SD. aaa,bbb,cccp < 0.001 as compared with the parameters of propofol-O-glucuronidation and G1 and G2 formation by UGT1A9, respectively. Propofol-G, G1, and G2 mean propofol-O-glucuronide, fraxetin-8-O-glucuronide, and fraxetin-7-O-glucuronide, respectively. Vmax, maximal velocity; Km, Michaelis constant; CLint, intrinsic clearance. MM, Michaelis–Menten model.