TABLE 4

Kinetic parameters of dex- and levomedetomidine glucuronidation by recombinant human UGT1A4 and UGT2B10 Data are presented as mean ± S.E. The assay conditions are detailed in the legend to Fig. 5.



UGT1A4

UGT2B10

Km
Vmaxa (normal)
n
Km
Vmaxa (normal)
Ksi
μM pmol/min/mg μM pmol/min/mg μM
Dexmedetomidine
   DG1 644 ± 132b 167 ± 17 1.25 10.8 ± 0.8c 3.3 ± 0.1
   DG2 706 ± 11c 24.3 ± 1.7 15.7 ± 1.5c 2.3 ± 0.1
Levomedetomidine
   LG1 312 ± 44c 17.7 ± 0.8 7.4 ± 0.6d 57.2 ± 1.5 1490 ± 190
   LG2
1600 ± 300c
29.7 ± 3.0

N.D.


  • N.D., activity below quantification limit (0.2 pmol/min/mg protein)

  • a Normalized Vmax values were calculated by dividing the Vmax value (picomoles per minute per milligram) by the relative expression level of the UGTs (UGT1A4 = 1.00, UGT2B10 = 0.51)

  • b The data were fitted to Hill equation (eq. 2; for further details, see Materials and Methods) using 1/v weighting

  • c The data were fitted to Michaelis-Menten equation (eq. 1; for further details, see Materials and Methods) using uniform weighting

  • d The data were fitted to substrate inhibition model (eq. 3; for further details, see Materials and Methods) using uniform weighting