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, ¹⁴C-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–∞ of total radioactivity were 36.2 and 47.1 µg eq. 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.

Key Words::

• Prasugrel
• thienopyridine
• distribution
• excretion