T. Shiga, M. Hashiguchi, Koichi Nakamura
Jul 31, 2013
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Rinsho Yakuri\/japanese Journal of Clinical Pharmacology and Therapeutics
Abstract
Pilsicainide hydrochloride is a class Ic antiarrhythmic agent that exhibits pure Na channel blocking action with slow kinetic recovery properties. Pilsicainide is effective for the termination and prevention of atrial fibrillation and is commonly used in Japan. Pilsicainide is mainly excreted in the urine, where approximately 80% of the compound is excreted in its unchanged form. We previously reported that pilsicainide is a cationic drug, and is excreted via the organic cationic transport system in the renal proximal tubule in humans. P-glycoprotein(P-gp)mediates the ATP-dependent export of many drugs and endogenous substrates from cells and is expressed in the luminal membrane of the small intestine and blood-brain barrier as well as in the apical membrane of excretory cells such as renal proximal tubule cells. P-glycoprotein substrates are generally organic cations or neutral molecules. Because pilsicainide is a cationic compound, it has been hypothesized that a P-gp-induced transport mechanism in addition to a cation transport mechanism may mediate the renal elimination of pilsicainide. However, we have shown that the potent P-gp inhibitor verapamil does not affect the renal elimination of pilsicainide in humans and that P-gp does not participate in the transcellular transport of pilsicainide from an experiment using P-gpexpressing renal tubular cells. 臨床薬理 Jpn J Clin Pharmacol Ther 2013 ; 44(4): 301-305 301