YJC-10592, a novel chemokine receptor 2 (CCR-2) antagonist, was developed for treating asthma and atopic dermatitis. We studied the pharmacokinetic characteristics of YJC-10592 after intravenous (5, 10 and 20 mg/kg) and oral (100 and 200 mg/kg) administration of the drug to rats. Tissue distribution of YJC-10592 was also evaluated after intravenous administration of YJC-10592, 10 mg/kg, to rats. The pharmacokinetics of YJC-10592 was dose-dependent from 20 mg/kg after intravenous administration to rats. The values of the area under the plasma concentration-time curve from time zero to infinity (AUC) of YJC-10592 were dose-dependent from 20 mg/kg and the time-averaged total body (CL) and nonrenal (CLNR) clearances of YJC-10592 were significantly lower at dose of 20 mg/kg, suggesting that saturable metabolism may be involved. The absolute bioavailability (F) of YJC-10592 was generally low (<2.55 %) for both oral doses due to incomplete absorption and low urinary excretion. YJC-10592 had a great affinity to all rat tissues studied except brain, which was supported by a relatively high value of the apparent volume of distribution at steady state (V ss) (890-1385 mL/kg). In conclusion, YJC-10592 showed dose-dependent pharmacokinetics and low F value due to slower elimination and incomplete absorption.
Keywords: CCR-2 antagonist; Dose-dependent; Pharmacokinetics; YJC-10592.