Effect of cimetidine and probenecid on pilsicainide renal clearance in humans

Tsuyoshi Shiga, Masayuki Hashiguchi, Akinori Urae, Hiroshi Kasanuki, Tadaaki Rikihisa

研究成果: Article査読

40 被引用数 (Scopus)

抄録

Objective: To investigate the effect of cimetidine and probenecid on the renal clearance of pilsicainide in healthy subjects. Methods: Nine healthy men (age range, 21 to 38 years) were given oral doses of 50 mg pilsicainide hydrochloride alone, with coadministration of 800 mg oral cimetidine, or with coadministration of 1500 mg oral probenecid on three occasions in a Latin- square order. Urine and venous blood samples were collected on a timely basis. The concentration of pilsicainide in plasma and urine were determined by an HPLC method. Results: Concomitant administration of cimetidine significantly increased the area under the plasma concentration-time curve of pilsicainide by a mean of 33%, prolonged elimination half-life by a mean of 24% (from 5 to 6.2 hours), reduced apparent oral clearance by a mean of 26% (from 14.7 ± 0.1 to 10.8 ± 0.8 L/h) and reduced renal clearance by a mean of 28% (from 196.8 ± 53.9 to 141.8 ± 25.9 mL/min). The net renal clearance by tubular secretion was significantly reduced by a mean value of 38%, from 151.4 ± 62.9 to 93.0 ± 31.1 mL/min. Coadministration of probenecid did not show any changes in plasma concentrations of pilsicainide, pharmacokinetics, or the net renal clearance by tubular secretion of pilsicainide. Conclusions: Pilsicainide appeared to be secreted by the active transport system for organic bases in the proximal tubule, and the excretion of pilsicainide was inhibited by cimetidine.

本文言語English
ページ(範囲)222-228
ページ数7
ジャーナルClinical Pharmacology and Therapeutics
67
3
DOI
出版ステータスPublished - 2000 1 1
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 薬理学(医学)

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