Table 2.

Pharmacokinetic profiles of CatK inhibitors in rabbits[13,25]

Compound	Dose (mg/kg)	AUC (μm*hr)	C max (nM)	C min (nM)	Cl (mL/min/kg)	[C min ]/bone res IC 50	IC 50 (nM)
							Rabbit CatK	Rabbit bone resorption assay
L-833905	10	1.9	163	29	–	0.2	33 ± 2	149 ± 20
	30	6.1	651	60		0.4
L-006235	1	0.3	74	9	113	1.8	0.5	5 ± 1
	3	1.0	337	15		3.0
	10	5.0	2436	8		1.6
L-873724	1	0.5	78	<LOD*	26	≤0.1	0.8	13 ± 1
	3	3.1	490	28		2.2
	10	7.8	1370	32		2.5
ODN	0.3	0.7	33	35	6	1.5	1.0	23 ± 6
	1	2.2	130	37		1.6
	3	4.1	270	88		3.8

* ~ 1 nM.

AUC = area under the curve, CatK = Cathepsin K, Cl = clearance, C_max = maximum concentration after dosing, C_min = minimum concentration after dosing, IC₅₀ = half maximal inhibitory concentration, LOD = limit of detection, ODN = odanacatib, res = resorption.

Reprinted (adapted) with permission from Falgueyret et al. 2005 [13].

Reprinted (adapted) with permission from Gauthier et al. 2008 [25].