TY - JOUR T1 - Species Differences in Pharmacokinetics of a Hepatoprotective Agent, YH439, and Its Metabolites, M4, M5, and M7, after Intravenous and Oral Administration to Rats, Rabbits, and Dogs JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 152 LP - 163 VL - 26 IS - 2 AU - Woo H. Yoon AU - Jung K. Yoo AU - Jong W. Lee AU - Chang-K. Shim AU - Myung G. Lee Y1 - 1998/02/01 UR - http://dmd.aspetjournals.org/content/26/2/152.abstract N2 - Pharmacokinetic parameters of YH439 and its metabolites, M4, M5, and M7, were compared after iv administration of YH439 to rats (1–10 mg/kg), rabbits (1–10 mg/kg), and dogs (1–20 mg/kg) and oral administration of YH439 to rats (50–500 mg/kg) and dogs (0.5–2 g per whole body weight). After oral administration of YH439 to rats, theF values were 3.67, 1.33, and 0.859% for YH439 oral doses of 100, 300, and 500 mg/kg, respectively. However, the Fvalue increased significantly, 21.2%, after oral administration of YH439-contained mixed micelles (10 mg as free YH439) to rats due to increased water solubility of YH439. Species differences in the pharmacokinetics of YH439 and its metabolites were found. First, M7 was detected in both plasma and urine after both iv and oral administration of YH439 to dogs, whereas it was detected neither in rats nor in rabbits, indicating that considerable amount of M7 was formed from YH439 only in dogs. Second, the AUC (or AUC0→t) ratios of M4 to YH439 after iv administration of YH439 were 24.6–31.3, 42.2–49.2, and 2200–7640% for rats, rabbits, and dogs, respectively, indicating that formation of M4 after iv administration of YH439 was maximal in dogs. Third, the AUC (or AUC0→t) ratios of M5 to YH439 after iv administration of YH439 were 103–127, 2.93–3.31, and 92.4–158% for rats, rabbits, and dogs, respectively, indicating that formation of M5 after iv administration of YH439 was minimal in rabbits. The American Society for Pharmacology and Experimental Therapeutics ER -