Tsuyoshi Shiga    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Visiting Professor
Article types	Original article
Language	English
Peer review	Non peer reviewed
Title	Lack of Contribution of P-Giycoprotein-Mediated Transport to Renal Excretion of Pilsicainide in Humans
Journal	Formal name：Japanese Journal of Clinical Pharmacology and Therapeutics Abbreviation：Jpn. J. Clin. Pharmacol. Ther. ISSN code：03881601/18828272
Domestic / Foregin	Domestic
Publisher	Japanese Society of Clinical Pharmacology and Therapeutics
Volume, Issue, Page	43(3),pp.157-164
Author and coauthor	SHIGA Tsuyoshi†, HASHIGUCHI Masayuki, TANAKA Takanori, MOROZUMI Naomi, IRIE Shin, MOCHIZUKI Mayumi, HAGIWARA Nobuhisa, KASANUKI Hiroshi
Authorship	Lead author
Publication date	2012/05
Summary	Pilsicainide is a cationic antiarrhythmic agent that has the potential of drug-drug interactions because of P-glycoprotein (P-gp)-mediated transport and organic cation transport of the drug in renal tubules. We evaluated the contribution of P-gp-mediated transport to renal clearance of pilsicainide in humans. A pharmacokinetic study conducted in 8 healthy female subjects (aged 29±4 years; body weight 49.8±5.2 kg) showed that verapamil (40 mg given three times a day), a potent P-gp inhibitor, did not significantly affect the renal clearance (pilsicainide alone: 224±34 versus pilsicainide+verapamil: 216±42 mL/min) or net renal clearance by tubular secretion (pilsicainide alone: 155±31 versus pilsicainide+verapamil: 148±35 mL/min) of pilsicainide after a single oral dose (50 mg). Using in vitro studies, pilsicainide stimulated little P-gp ATPase activity in human P-gp-expressing cell membranes. In addition, no concentration dependence was observed in the transcellular basolateral to apical transport of pilsicainide, and the P-gp substrates doxorubicin and vinblastine did not competitively inhibit pilsicainide transport in human P-gp-expressing LLC-GA5-COL150 cells. In conclusion, our results suggest that P-gp-mediated transport has minimal or no contribution to renal tubular secretion of pilsicainide in humans.
DOI	http://doi.org/10.3999/jscpt.43.157