<b>Lack of Contribution of P-Glycoprotein-Mediated Transport to Renal Excretion of Pilsicainide in Humans</b> Lack of Contribution of P-Glycoprotein-Mediated Transport to Renal Excretion of Pilsicainide in Humans

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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.

収録刊行物

  • 臨床薬理 = Japanese journal of clinical pharmacology

    臨床薬理 = Japanese journal of clinical pharmacology 43(3), 157-164, 2012-05-31

    The Japanese Society of Clinical Pharmacology and Therapeutics

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各種コード

  • NII論文ID(NAID)
    10030763575
  • NII書誌ID(NCID)
    AN0025404X
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    03881601
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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