TABLE 1

Summary of substrate depletion kinetics of CJ-13,610 and enzyme kinetic parameters for the sulfoxidation metabolic pathway in rat, dog, and human liver microsomes

Numbers in parentheses indicate S.E. of nonlinear regression analysis. Reaction velocities were estimated as described under Materials and Methods.

	Rat	Dog	Human
Substrate depletion
In vitro half-life (min)	26	71	28
f_u(plasma)	0.07	0.12	0.13
f_{u(microsomes)}	0.81	0.79	0.83
CL_int (μl/min/mg microsomal protein)	54	19	31
Predicted CL_h (ml/min/kg)^{^a}	40.6	16.5	11.7
Predicted CL_h (ml/min/kg)^{^b}	6.2	3.1	3.1
Predicted CL_h (ml/min/kg)^{^c}	7.4	3.8	3.6
CL_plasma (ml/min/kg)	11.5	4.4
Enzyme kinetics (CJ-13,610 sulfoxidation)
K_{m, app} (μM)	4.1 (0.55)	5.4 (0.32)	4.8 (0.59)
V_max (pmol/min/mg protein)	247 (8.1)	77.9 (1.1)	184 (5.4)
CL′_int (μl/min/mg microsomal protein)^{^d}	60	14	38

↵a No plasma or microsomal binding correction (eq. 1).
↵b Corrected for plasma protein binding only (eq. 1).
↵c Corrected for both plasma and nonspecific microsomal binding (eq. 1).
↵d Calculated using eq. 3.