TABLE 4.
Summary of pharmacokinetic parameters in CD-1 male mice for Cz007 and the diastereomeric mixture of Cz008 (Cz005)a
| Compound | Route | Vehicle | Dose (mg/kg) | Cmax (nM) | Tmax (h) | AUC (nM · h) | Clearance (ml/min/kg) | t1/2 (h) | Vd (liter/kg) | %F |
|---|---|---|---|---|---|---|---|---|---|---|
| Cz007 | p.o. | 0.5% Methocel | 20 | 1,350 | 1.5 | 6,400 | ||||
| i.v. | 60% PEG 200 | 5 | 3,600 | 37 | 1.1 | 3.7 | 45 | |||
| Cz005b | p.o. | 1% Methocel | 10 | 500 | 2 | 6,600 | ||||
| i.v. | 60% PEG 200 | 2 | 2,700 | 25 | 4.3 | 7.0 | 51 |
a
Animal were evaluated in groups of 2 (for Cz007) or 3 (for Cz005). Mice weighed approximately 25 g. Abbreviations: p.o., per os; i.v., intravenous; PEG 200, polyethylene glycol 200; Cmax, maximum concentration of drug in blood; Tmax, time to maximum concentation of drug in blood; t1/2, half-life; Vd, volume of distribution; %F, percent bioavailability.
b
Cz005 is a mixture of Cz008 and its diastereomer at the trifluoromethyl side chain position.