QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: dmd.107.016030v1 35/9/1624    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ohmori, S. Articles by Ooie, T. Search for Related Content PubMed PubMed Citation Articles by Ohmori, S. Articles by Ooie, T.

Absorption, Metabolism, and Excretion of [¹⁴C]Imidafenacin, a New Compound for Treatment of Overactive Bladder, After Oral Administration to Healthy Male Subjects

Research Center, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan (S.O., M.M., C.T., T.O.); and ADME/TOX Research Institute, Daiichi Pure Chemicals Co., Ltd., Ibaraki, Japan (Y.S.)

The absorption, metabolism, and excretion of imidafenacin [KRP-197/ONO-8025, 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide], a new antimuscarinic drug developed for treatment of overactive bladder, were assessed in six healthy male subjects after a single oral administration of 0.25 mg of [¹⁴C]imidafenacin (approximately 46 µCi). The highest radioactivity in the plasma was observed at 1.5 h after administration. The apparent terminal elimination half-life of the total radioactivity was 72 h. Approximately 65.6 and 29.4% of the administered radioactivity were recovered in the urine and feces, respectively, within 192 h after administration. The metabolite profiling by high-performance liquid chromatography-radiodetector and liquid chromatography/tandem mass spectrometry demonstrated that the main component of radioactivity was unchanged imidafenacin in the 2-h plasma. The N-glucuronide conjugate (M-9) was found as the major metabolite and the oxidized form of the 2-methylimidazole moiety (M-2) and the ring-cleavage form (M-4) were detected as the minor metabolites in the 2-h plasma, but M-4 was found to be the main component in the 12-h plasma. Unchanged imidafenacin, M-9, M-2, and other oxidized metabolites were excreted in the urine, but the unchanged imidafenacin and M-9 were not found in the feces. Two unique metabolites were found in the urine and feces, which were identified as the interchangeable cis- and trans-isomers of 4,5-dihydrodiol forms of the 2-methylimidazole moiety. These findings indicate that imidafenacin is rapidly and well absorbed (at least 65% of dose recovered in urine) after oral administration, circulates in human plasma as the unchanged form, its glucuronide, and other metabolites, and is then excreted in urine and feces as the oxidized metabolites of 2-methylimidazole moiety.

This article has been cited by other articles:

				T. Ohno, K. Nakayama, S. Nakade, J. Kitagawa, S. Ueda, H. Miyabe, Y. Miyata, and A. Ohnishi Effect of Itraconazole on the Pharmacokinetics of Imidafenacin in Healthy Subjects J. Clin. Pharmacol., March 1, 2008; 48(3): 330 - 334. [Abstract] [Full Text] [PDF]