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 Sourcefu,incKm,uVmaxClint,uClint,organ
µMpmol/min/mg proteinµl/min/mg micsl/h per organ
Cabotegravir
 HLMs0.52350 (41)705 (35)2.08.1
 HIMs0.69NDa1031 (323)NDaNDa
 HKMs0.50560 (57)1088 (56)1.90.45
Dolutegravir
 HLMs0.2332 (2)601 (13)1876
 HIMs0.3796 (7)1170 (33)122.1
 HKMs0.2947 (8)291 (16)6.21.1
Raltegravir
 HLMs1183 (23)1737 (63)9.538.7
 HIMs1167 (23)326 (13)2.00.3
 HKMs0.97493 (59)2332 (111)4.70.5
  • 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.