Table 1

Kinetics of glucuronidation in rat, dog, and human liver microsomes

Substrate	Human Liver Microsomes		Dog Liver Microsomes		Rat Liver Microsomes
Substrate	K_m	V_max	V_max/K_m	K_m	V_max	V_max/K_m	K_m	V_max	V_max/K_m
	μM	nmol/min/mg protein	μl/min/mg protein	μM	nmol/min/mg protein	μl/min/mg protein	μM	nmol/min/mg protein	μl/min/mg protein
4-Arylalkyl-1H-imidazoles
Levomedetomidine	16^1-a	1.89^1-a	117.0	279 ± 24	0.54 ± 0.03	1.9		N.D.
Dexmedetomidine	371	0.74	2.0	1150 ± 140	0.29 ± 0.04	0.3		N.D.
Detomidine	78 ± 13	1.22 ± 0.03	16.0	985 ± 195	0.39 ± 0.04	0.4		N.D.
Atipamezole	4.0 ± 0.9	1.02 ± 0.10	256.0	1050 ± 80	0.48 ± 0.03	0.5		0.001^1-b
MPV-207 A IV	34 ± 1	1.66 ± 0.06	48.0	1640 ± 300	0.69 ± 0.08	0.4		N.D.
MPV-295 A IV	31 ± 2	0.59 ± 0.02	19.0	503	0.73	1.4		0.004^1-b
Phenolic compounds
4-Nitrophenol	290 ± 16^1-a	30.6 ± 2.3^1-a	106.0	269 ± 27	195 ± 4	726.0	628 ± 15	66.6 ± 3.9	106.0
Amines
4-Aminobiphenyl	265 ± 35	5.07 ± 0.40	19.0	19 ± 1	0.52 ± 0.03	28.0	963	1.67	1.7
Amitriptyline	728	0.56	0.8		N.D.			N.D.
Nortriptyline		N.D.			N.D.			N.D.

All parameters represent an average ± S.D. of three to four replicate series or an average of two replicate series using a minimum of seven substrate concentration levels. Samples were prepared as described under Materials and Methods.

N.D., indicates that glucuronide formation was not detectable (detection limit 0.8 pmol/min/mg of protein).
↵1-a These results were published inKaivosaari et al., 2001.
↵1-b UGT activity at 500 μM substrate concentration rather than V_max. Glucuronidation assays of 4-arylalkyl-1H-imidazoles by rat liver microsomes (n = 2) were conducted at 37°C for 60 min with 500 μM substrate, 1.59 mg/ml microsomal protein, and 0.05 mg/ml Triton X-100.