TABLE 1.
Glucuronidation kinetic parameters from pooled human microsomal preparations
Values represent the parameter estimate (S.E.) by fitting substrate concentration to the simple Michaelis-Menten equation (v = Vmax *[S]/Km + [S]) to metabolite formation velocity using Phoenix WinNonlin (version 7.0). Clint calculated as the ratio of Vmax to Km.
| Enzyme Source |
fu,inc |
Km,u |
Vmax |
Clint,u |
Clint,organ |
|---|---|---|---|---|---|
| µM | pmol/min/mg protein | µl/min/mg mics | l/h per organ | ||
| Cabotegravir | |||||
| HLMs | 0.52 | 350 (41) | 705 (35) | 2.0 | 8.1 |
| HIMs | 0.69 | NDa | 1031 (323) | NDa | NDa |
| HKMs | 0.50 | 560 (57) | 1088 (56) | 1.9 | 0.45 |
| Dolutegravir | |||||
| HLMs | 0.23 | 32 (2) | 601 (13) | 18 | 76 |
| HIMs | 0.37 | 96 (7) | 1170 (33) | 12 | 2.1 |
| HKMs | 0.29 | 47 (8) | 291 (16) | 6.2 | 1.1 |
| Raltegravir | |||||
| HLMs | 1 | 183 (23) | 1737 (63) | 9.5 | 38.7 |
| HIMs | 1 | 167 (23) | 326 (13) | 2.0 | 0.3 |
| HKMs | 0.97 | 493 (59) | 2332 (111) | 4.7 | 0.5 |
a
The substrate concentration versus velocity did not saturate, and the estimated Km (>6 mM) and Vmax values were unreliable. Thus, the values are not presented, and Clint,u and Clint,organ were not determined (ND).
Micr, microsomal protein.