TABLE 3
Glucuronidation kinetic parameters from UGT overexpression in HEK cell system
Values represent the parameter estimate (S.E.) by fitting substrate concentration to the simple Michaelis-Menten (MM) or Hill equation, as described in the Materials and Methods, to metabolite formation velocity using Phoenix WinNonlin (version 7.0).
| Enzyme Source | Model | Km,u or S50,u | Vmax | n | Clint,u or Clmax,u |
|---|---|---|---|---|---|
| µM | pmol/min/mg total protein | µl/min/mg protein | |||
| Cabotegravir | |||||
| HEKUGT1A1 | MM | 55 (9) | 7 (0) | 0.1 | |
| HEKUGT1A7 | MM | 23 (6) | 9 (0) | 0.3 | |
| HEKUGT1A8 | MM | 133 (5) | 12 (0) | 0.09 | |
| HEKUGT1A9 | MM | 163 (6) | 25 (0) | 0.2 | |
| Dolutegravir | |||||
| HEKUGT1A1 | MM | 96 (15) | 21 (1) | 0.2 | |
| HEKUGT1A7 | Hill | 2 (3) | 2 (0) | 1.4 (0) | 1.1 |
| HEKUGT1A8 | Hill | 37 (2) | 36 (1) | 1.4 (0) | 1.0 |
| HEKUGT1A9 | Hill | 46 (3) | 107 (4) | 1.7 (0) | 2.3 |
| Raltegravir | |||||
| HEKUGT1A1 | Hill | 52 (7) | 17 (1) | 1.5 (0) | 0.4 |
| HEKUGT1A3 | Hill | 22 (1) | 2 (0) | 1.7 (0) | 0.05 |
| HEKUGT1A7 | MM | 79 (8) | 6 (0) | 0.07 | |
| HEKUGT1A8 | Hill | 142 (15) | 6 (0) | 1.4 (0) | 0.1 |
| HEKUGT1A9 | Hill | 219 (29) | 24 (1.4) | 1.5 (0) | 0.06 |
Clint = Vmax/Km or Clmax =
. n, Hill coefficient in the Hill equation.
