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KMID : 0043320160390060833
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Archives of Pharmacal Research
2016 Volume.39 No. 6 p.833 ~ p.842
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Pharmacokinetics of YJC-10592, a novel chemokine receptor 2 (CCR-2) antagonist, in rats
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Du Eun-Sin
Moon Hong-Sik
Lim Soo-Jeong
Kim So-Hee
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Abstract
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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 (Vss) (890?1385 mL/kg). In conclusion, YJC-10592 showed dose-dependent pharmacokinetics and low F value due to slower elimination and incomplete absorption.
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KEYWORD
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YJC-10592, CCR-2 antagonist, Pharmacokinetics, Dose-dependent
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