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Pharmacokinetics of bretylium in man after intravenous administration

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Abstract

The pharmacokinetic profile of bretylium was studied in four normal male volunteers using a new sensitive EC-GC procedure for its quantitation in biological fluids. The plasma concentrations and urinary excretion rates following the constant i.v. infusion of a single 4mg/kg dose of bretylium tosylate declined biexponentially and the data were fitted to a two-compartment model with a renal and a nonrenal route of elimination. The drug had a mean half-life (t1/2β)of 7.8 hr and apparent volume of distribution (Vd,β)of 8.18 liters/kg. The renal clearance, which was 6 times that of the glomerular filtration rate, accounted for almost 84% of the total body clearance and correlated linearly with the subjects' creatinine clearance. The observed side effects of bretylium were mild and similar to those of other adrenergic blocking agents.

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Author notes

  1. Joseph Adir

    Present address: Stauffer Chemical Company, 06032, Farmington, Connecticut

Authors and Affiliations

  1. Clinical Pharmacokinetics Laboratory, Department of Pharmaceutics, School of Pharmacy, University of Maryland, 21201, Baltimore, Maryland

    Prem K. Narang & Joseph Adir

  2. Division of Nephrology, Department of Internal Medicine, University of Maryland, 21201, Baltimore, Maryland

    John Josselson & John Sadler

  3. Arnar-Stone Laboratories, Inc., 60085, McGaw Park, Illinois

    Avraham Yacobi

Authors
  1. Prem K. Narang
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  2. Joseph Adir
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  3. John Josselson
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  4. Avraham Yacobi
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  5. John Sadler
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Additional information

This work was supported in part by a grant from Arnar-Stone Laboratories, Inc., McGaw Park, Illinois.

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Narang, P.K., Adir, J., Josselson, J. et al. Pharmacokinetics of bretylium in man after intravenous administration. Journal of Pharmacokinetics and Biopharmaceutics 8, 363–372 (1980). https://doi.org/10.1007/BF01059384

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  • DOI: https://doi.org/10.1007/BF01059384

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