Table 1.

Enzyme kinetic parameter estimates (mean ± standard deviation for 3 independent experiments) determined for formation of mycophenolic acid phenol glucuronide, acyl glucuronide, and phenol glucoside by pooled liver microsomes from cats (n = 16), dogs (n = 26), and humans (n = 48). Also shown are the results of statistical comparisons between CLint values for cats compared with values for dogs and humans by ANOVA.

Species	Metabolite formed	Vmax (nmoles/min/mg)	Km (µM)	CLint* (mL/kg/min)	CLint** (% total)
Cats	Phenol glucuronide	1.67 ± 1.31	510 ± 320	3.41 ± 1.171	23 ± 3
	Acyl glucuronide	0.67 ± 0.17	327 ± 180	2.48 ± 1.242	17 ± 7
	Phenol glucoside	0.64 ± 0.29	84 ± 59	8.6 ± 2.43	60 ± 8
	Total conjugation:			15 ± 44
Dogs	Phenol glucuronide	5.21 ± 2.33	280 ± 171	19.8 ± 4.0	56 ± 4
	Acyl glucuronide	2.9 ± 1.0	854 ± 355	3.45 ± 0.65	10 ± 1
	Phenol glucoside	2.7 ± 0.55	228 ± 50	12 ± 0.2	34 ± 5
	Total conjugation:			35 ± 4
Humans	Phenol glucuronide	6.86 ± 1.72	308 ± 130	23.4 ± 4.5	91 ± 2
	Acyl glucuronide	0.99 ± 0.44	597 ± 294	1.68 ± 0.09	7 ± 1
	Phenol glucoside	0.18 ± 0.10	364 ± 72	0.49 ± 0.19	2 ± 1
	Total conjugation:			26 ± 4

^*CLint = intrinsic clearance calculated by dividing the Vmax by the Km estimates.

^**CLint for each activity expressed as a percentage of the total summed CLint values for all activities within each species.

¹Phenol glucuronidation CLint of MPA in cats was only 17% that of dogs (p = 0.002, Dunnett’s test) and only 15% that of humans (p < 0.001, Dunnett’s test).

²Acyl glucuronidation CLint of MPA in cats was not different from other species (p > 0.05, ANOVA).

³Phenol glucosidation CLint of MPA in cats was over 20 times that of humans (p<0.001, Dunnett’s test) but similar to that of dogs (p > 0.05, Dunnett’s test).

⁴Total conjugation for cats was 43% that of dogs (p = 0.002, Dunnett’s test) and 58% that of humans (p = 0.033, Dunnett’s test).