TABLE 4

Bupropion glucuronidation kineticsa

SubstrateKm or S50 (µM)VmaxClintd or Clmaxe
μMpmol/min/mgµl/min/mg
(S,S)-hydroxybupropion glucuronidea172 ± 38.9739 ± 59.64.31
(R,R)-hydroxybupropion glucuronidea488 ± 98.35550 ± 50711.4
(1R,2R)-hydrobupropion glucuronideb343 ± 37.53290 ± 2697.7
(1S,2S)-hydrobupropion glucuronideb248 ± 27.1358 ± 25.51.1
EGLUC1c373 ± 63.01740 ± 2123.1
EGLUC2c360 ± 55.22280 ± 2413.8
  • Values represent the parameter estimate ± S.E. obtained by fitting the Michaelis-Mentena (hydroxybupropion) or Hill.

  • b Glucuronide 1 and glucuronide 2 denoted based on retention times in Figs. 13 and outlined in Table 2. Erythro-hydrobupropion glucuronide (EGLUC).

  • c (threo- and erythro-hydrobupropion) equation to [substrate] versus metabolite formation velocity using Phoenix WinNonlin (version 6.4).

  • d Intrinsic clearance (Clint), calculated as the ratio of Vmax to Km.

  • e Maximal clearance (Clmax), calculated as the ratio of Vmax × (h − 1) to S50 + h(h − 1)1/h.