title: Pharmacokinetic disposition of anagliptin, a novel dipeptidyl peptidase-4 inhibitor, in rats and dogs.
abstract: The pharmacokinetic disposition of anagliptin, an orally active and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor was evaluated in male rats and dogs. Anagliptin was well absorbed in dogs (70.4 %) and moderately to well absorbed in rats ranging from 38.1 to 85.5 % depending on the dose. In situ testing indicated that anagliptin absorption from rat intestine was apparently limited by P-glycoprotein. The absorbed radioactivity was distributed rapidly throughout the body, and high levels of radioactivity were found in the tissues expressing DPP-4 at high levels, especially small intestine, kidney and liver. In both species, the major circulating component was unchanged anagliptin; major circulating metabolites were M1 resulting from hydrolysis of the cyano group and M6 and M7, both of which resulting from the oxidation-cleavage of the methylene function adjacent to the amine. After intravenous dosing, urinary excretion of radioactivity was the major route of elimination for rats (64.6 %) and dogs (66.2 %), and biliary excretion was demonstrated to be an important pathway in rats (25.2 %). The total recovery was good (97.5-99.5 %) and most of the radioactivity was excreted by 24 h in both species. The renal clearance of unbound anagliptin in rats (91.7 ml/min/kg) was much higher than the glomerular filtration rate, indicative of active renal elimination.
authors: Pharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho, Co. Ltd, 363 Shiosaki, Hokusei-cho, Inabe, Mie, 511-0406, Japan, s_furuta@mb4.skk-net.com.
authors: Shinji
authors: S
authors: Furuta
authors: Miyuki
authors: M
authors: Tamura
authors: Hiroko
authors: H
authors: Hirooka
authors: Yukie
authors: Y
authors: Mizuno
authors: Mika
authors: M
authors: Miyoshi
authors: Yoshiyuki
authors: Y
authors: Furuta
mesh_terms: D000818:Animals; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics*; D004285:Dogs; D008297:Male; D011743:Pyrimidines / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011743:Pyrimidines; C583175:anagliptin