シガ ツヨシ   Tsuyoshi Shiga
  志賀 剛
   所属   医学部 医学科(東京女子医科大学病院)
   職種   客員教授
論文種別 原著
言語種別 英語
査読の有無 査読なし
表題 Lack of Contribution of P-Giycoprotein-Mediated Transport to Renal Excretion of Pilsicainide in Humans
掲載誌名 正式名:Japanese Journal of Clinical Pharmacology and Therapeutics
略  称:Jpn. J. Clin. Pharmacol. Ther.
ISSNコード:03881601/18828272
掲載区分国内
出版社 Japanese Society of Clinical Pharmacology and Therapeutics
巻・号・頁 43(3),157-164頁
著者・共著者 SHIGA Tsuyoshi†, HASHIGUCHI Masayuki, TANAKA Takanori, MOROZUMI Naomi, IRIE Shin, MOCHIZUKI Mayumi, HAGIWARA Nobuhisa, KASANUKI Hiroshi
発行年月 2012/05
概要 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