title: Absorption, distribution and excretion of the new thienopyridine agent prasugrel in rats.
abstract: Prasugrel is converted to the pharmacologically active metabolite after oral dosing in vivo. In this study, (14)C-prasugrel or prasugrel was administered to rats at a dose of 5 mg kg(-1). After oral and intravenous dosing, the values of AUC(0-infinity) of total radioactivity were 36.2 and 47.1 microg eqx h ml(-1), respectively. Oral dosing of unlabeled prasugrel showed the second highest AUC(0-8) of the active metabolite of six metabolites analyzed. Quantitative whole body autoradiography showed high radioactivity concentrations in tissues for absorption and excretion at 1 h after oral administration, and were low at 72 h. The excretion of radioactivity in the urine and feces were 20.2% and 78.7%, respectively, after oral dosing. Most radioactivity after oral dosing was excreted in bile (90.1%), which was reabsorbed moderately (62.4%). The results showed that orally administered prasugrel was rapidly and fully absorbed and efficiently converted to the active metabolite with no marked distribution in a particular tissue.
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan. hagihara.katsunobu.fc@daiichisankyo.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Hagihara
authors.forename: A
authors.initials: A
authors.lastname: Kurihara
authors.forename: K
authors.initials: K
authors.lastname: Kawai
authors.forename: M
authors.initials: M
authors.lastname: Kazui
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Kawabata
authors.forename: N A
authors.initials: NA
authors.lastname: Farid
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D007408:Intestinal Absorption; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics*; D000068799:Prasugrel Hydrochloride; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D013876:Thiophenes / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines; D013876:Thiophenes; C446540:thienopyridine; D000068799:Prasugrel Hydrochloride