Effect of cimetidine and probenecid on pilsicainide renal clearance in humans

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

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Abstract

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.

Original languageEnglish
Pages (from-to)222-228
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume67
Issue number3
Publication statusPublished - 2000
Externally publishedYes

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Probenecid
Cimetidine
Kidney
Urine
pilsicainide
Active Biological Transport
Half-Life
Healthy Volunteers
Pharmacokinetics
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of cimetidine and probenecid on pilsicainide renal clearance in humans. / Shiga, Tsuyoshi; Hashiguchi, Masayuki; Urae, Akinori; Kasanuki, Hiroshi; Rikihisa, Tadaaki.

In: Clinical Pharmacology and Therapeutics, Vol. 67, No. 3, 2000, p. 222-228.

Research output: Contribution to journalArticle

Shiga, Tsuyoshi ; Hashiguchi, Masayuki ; Urae, Akinori ; Kasanuki, Hiroshi ; Rikihisa, Tadaaki. / Effect of cimetidine and probenecid on pilsicainide renal clearance in humans. In: Clinical Pharmacology and Therapeutics. 2000 ; Vol. 67, No. 3. pp. 222-228.
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AB - 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.

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