Table 2.

In vitro and in vivo PK.

Compd	aLog D pH 7.4	LEb	intrinsic Clintc		rat pKd
			mouse (µL/min/mg protein)	human (µL/min/mg protein)	AUC po ng·min mL−1	Cl mL/kg/min	F%
5	1.7	0.45	127	18	ND	ND	ND
15	2.8	0.41	83	26	1674	2	0.3
16	2.6	0.45	91	16	ND	ND	ND
18	1.7	0.51	38	14	74,396	1.6	12
31	1.6	0.36	8	4	7,83,782	1	81
39	2.6	0.43	31	–	43,569	10	39
49	1.7	0.47	41	11	–	–	–
51	1.0	0.44	9	12	50,940	3	13

^aMeasured by octanol/buffer shake flask method at pH 7.4 (see Supplementary data file for details).²⁰

^bLE values were calculated by LE = (RT ln K_d)/N, presuming EC₅₀ ≈ K_d.¹⁸

^cIntrinsic clearance Cl_int data for screening purposes only: Mouse and Human microsomes were incubated with the test compound at 37 °C in the presence of the co-factor, NADPH. The data is the mean of 5 separate experiments. Compound disappearance monitored over 45 min period. SEM is less than 10% of the mean values.

^dRat PK (n = 4): AUC (ng·min mL⁻¹) at 10 mg/kg, 8% Ethanol/92% PEG-400 formulation, Cl in mL min⁻¹ kg⁻¹. ND = not determined.