title: Pharmacokinetics of YJC-10592, a novel chemokine receptor 2 (CCR-2) antagonist, in rats.
abstract: 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.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, San 5, Woncheon-dong, Yeongtong-gu, Suwon, 443-749, South Korea.
authors.forename: Eun Sin
authors.initials: ES
authors.lastname: Du
authors.affiliation: Yang-Ji Chemical Company, Suwon, South Korea.
authors.forename: Hong Sik
authors.initials: HS
authors.lastname: Moon
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Seoul, South Korea.
authors.forename: Soo-Jeong
authors.initials: SJ
authors.lastname: Lim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, San 5, Woncheon-dong, Yeongtong-gu, Suwon, 443-749, South Korea. shkim67@ajou.ac.kr.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001549:Benzamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D055808:Drug Discovery; D004355:Drug Stability; D007275:Injections, Intravenous; D008297:Male; D015394:Molecular Structure; D009928:Organ Specificity; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution
chemical_list: D000081:Acetamides; D018927:Anti-Asthmatic Agents; D001549:Benzamides; D001798:Blood Proteins; D054390:Receptors, CCR2; C000613909:YJC-10592
keywords: CCR-2 antagonist; Dose-dependent; Pharmacokinetics; YJC-10592