TABLE 2

Pharmacokinetics of JM6 and Ro-61-8048 in mice after oral administration alone or in combination

Group	Analyte Dosed (Dose Level)	Analyte Measured	AUC_last	AUC_inf	AUCN	F	C_max	C_maxN	T_max	t_1/2
			nM × h		nM × h × kg/mg	%	nM		h
I	JM6 (10 mg/kg)^{^a}	JM6	1100	1100	110	7.2	100	110	0.5	1.1
		Ro-61-8048	2000	2300	N.C.	N.C.	230	N.C.	4.0^{^b}	6.6
II	Ro-61-8048 (0.05 mg/kg) with JM6 (9.5 mg/kg)^{^a}	JM6	1500	1500	160	9.8	1400	150	0.5	0.9
		Ro-61-8048	49,000	53,000	110,000	N.C.	9000	18,000	0.5^{^b}	6.9
III	Ro-61-8048 (1.0 mg/kg) with JM6 (9.0 mg/kg)	JM6	1100	1100	130	7.8	1000	110	0.5	0.7
		Ro-61-8048	110,000	110,000	140,000	N.C.	17,000	21,000	0.5^{^b}	4.4
IV	Ro-61-8048 (0.05 mg/kg) alone	Ro-61-8048	4300	4500	90,000	70	550	11,000	0.5^{^b}	5.2
V	Ro-61-8048 (0.05 mg/kg) with JM6 (10 mg/kg)^{^a}	JM6	1300	1300	130	13	1900	190	0.5	0.7
		Ro-61-8048	4900	5200	100,000	80	530	11,000	1.0^{^b}	5.8
VI	Ro-61-8048 (0.05 mg/kg) with JM6 (25 mg/kg)^{^a}	JM6	4800	4800	190	N.C.	3400	140	0.5	0.7
		Ro-61-8048	8400	8800	180,000	N.C.	800	16,000	2.0^{^b}	5.2
VII	Ro-61-8048 (0.05 mg/kg) with JM6 (50 mg/kg)^{^a}	JM6	9600	9600	190	N.C.	8100	190	0.5	0.7
		Ro-61-8048	7900	N.C.	160,000	N.C.	19,000	160,000	4.0^{^b}	6.5

N.C., not calculated.
↵a JM6 in the dose contained <0.4% of Ro-61-8048.
↵b The T_max for Ro-61-8048 is observed between 0.5 and 4 h and is difficult to define precisely in nonserial studies because of the leveled protracted plasma concentration versus time curve driven by the slow Cl_p.