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 SourceModelKm,u or S50,uVmaxnClint,u or Clmax,u
µMpmol/min/mg total proteinµl/min/mg protein
Cabotegravir
 HEKUGT1A1MM55 (9)7 (0)0.1
 HEKUGT1A7MM23 (6)9 (0)0.3
 HEKUGT1A8MM133 (5)12 (0)0.09
 HEKUGT1A9MM163 (6)25 (0)0.2
Dolutegravir
 HEKUGT1A1MM96 (15)21 (1)0.2
 HEKUGT1A7Hill2 (3)2 (0)1.4 (0)1.1
 HEKUGT1A8Hill37 (2)36 (1)1.4 (0)1.0
 HEKUGT1A9Hill46 (3)107 (4)1.7 (0)2.3
Raltegravir
 HEKUGT1A1Hill52 (7)17 (1)1.5 (0)0.4
 HEKUGT1A3Hill22 (1)2 (0)1.7 (0)0.05
 HEKUGT1A7MM79 (8)6 (0)0.07
 HEKUGT1A8Hill142 (15)6 (0)1.4 (0)0.1
 HEKUGT1A9Hill219 (29)24 (1.4)1.5 (0)0.06
  • Clint = Vmax/Km or Clmax = Embedded Image. n, Hill coefficient in the Hill equation.