Absorption, distribution and excretion of the new thienopyridine agent prasugrel in rats.
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.
Hagihara
K
K
Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan. hagihara.katsunobu.fc@daiichisankyo.co.jp
Kurihara
A
A
Kawai
K
K
Kazui
M
M
Takahashi
M
M
Kawabata
K
K
Farid
N A
NA
Ikeda
T
T
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*
D002250:Carbon Radioisotopes; D010879:Piperazines; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines; D013876:Thiophenes; C446540:thienopyridine; D000068799:Prasugrel Hydrochloride