Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis

Table 2 Modeled Human Pharmacokinetic Parameters and JAK1/3 and JAK2 IC₅₀ Coverage for CP-690,550

BID Dose mg	Cmax (nM)	24 hr AUC (nM*h)	JAK1/3 IC₅₀Coverage Every 12 hrs^A (range^B)	JAK2 IC₅₀Coverage Every 12 hrs^{C, D} (range)
5	167	1548	7.8 hrs (7.0-8.8)	0 hrs^C (0-0) 0 hrs^D
10	337	3097	10.3 hrs (9.6-11.3)	0 hrs (0-0) 0.3 hrs
15	503	4645	11.7 hrs (10.9-12.0)	0 hrs (0-0) 2.1 hrs
30	1006	9291	12.0 hrs (12.0-12.0)	0 hrs (0-0) 5.0 hrs

^A JAK1/3 human whole blood IC₅₀ (IL-21 dependent pSTAT3) = 25 ± 6 nM; ^B range based on the upper and lower error around the IC₅₀ where available; ^C JAK2 human whole blood IC₅₀ (GM-CSF dependent pSTAT5) = 1377 ± 185 nM; ^D GM-CSF stimulated myelomonocytic HUO3 cell JAK2 IC₅₀ = 324 nM [1].

ISSN: 1476-9255