TABLE 3

Pharmacokinetic parameters of indomethacin-amides 1 to 4 in male Sprague-Dawley rats

Compounds were administered via intravenous bolus to fasted male Sprague-Dawley rats (n = 3) in 95% glycerol formal containing 5% DMSO. For oral studies, compounds were administered via gavage to fasted male Sprague-Dawley rats (n = 3) as a suspension in 0.5% methyl cellulose.

Compound	Dose	Route	C_max	T_max	CL_p	V_dss	AUC_0—∞	T_1/2	F
	mg/kg		ng/ml	h	ml/min/kg	l/kg	ng · h/ml	h	%
Amide 1	1.0	i.v.			155 ± 41.5	5.3 ± 1.2	114 ± 35.0	0.6 ± 0.1
	5.0	p.o.	N.C.	N.C.			N.C.		N.C.
Amide 2	1.0	i.v.			26.0 ± 9.40	2.3 ± 1.1	699 ± 240	1.1 ± 0.3
	5.0	p.o.^a	57.0	3.0			677		20
Amide 3	1.0	i.v.			39.2 ± 4.50	2.0 ± 0.4	430 ± 49.0	1.0 ± 0.3
	5.0	p.o.	120 ± 55.8	1.2 ± 0.7			828 ± 490		38.5
Amide 4	1.0	i.v.			31.0 ± 7.00	0.7 ± 0.2	562 ± 150	1.4 ± 0.4
	5.0	p.o.	154 ± 42.1	1.0 ± 0.8			1060 ± 167		37.6
Indomethacin^b	1.0	i.v.			0.51 ± 0.04	0.19 ± 0.03		4.6 ± 1.0

N.C., not calculated [systemic exposure below the lower limit of quantitation (5 ng/ml)].
↵ a n = 2 rats.
↵ b Intravenous pharmacokinetic data from Paine et al. (2008).