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Bretylium kinetics in renal insufficiency
Author(s) -
Josselson John,
Narang Prem K,
Adir Joseph,
Yacobi Avraham,
Sadler John H
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.22
Subject(s) - bretylium , renal function , urology , creatinine , hemodialysis , volume of distribution , pah clearance , medicine , extraction ratio , dialysis , clearance , endocrinology , chemistry , pharmacokinetics , renal blood flow , effective renal plasma flow , adrenergic , chromatography , receptor , extraction (chemistry)
Bretylium kinetics were examined in patients with varying degrees of renal impairment after a single intravenous dose of bretylium tosylate. Maximum plasma concentrations achieved at the end of the infusion, when normalized to the dose, correlated strongly with creatinine clearance. Drug disposition from plasma was biexponential, with a short distributive phase, but drug elimination was reduced, especially in patients with creatinine clearance below 30 ml/min · 1.73 m 2 . There was reduction in renal and total clearance and prolongation of t½, with deteriorating renal function. In one patient who was reevaluated after a year, there was 76% reduction in the total clearance, corresponding to 43% deterioration of renal function. The difference of 33% between these values is due to a reduction of nearly 36% in volume of distribution, caused by the further deterioration of the renal function. Six‐hour hemodialysis procedure on two anephric patients, resulted in an apparent one‐ to threefold increase in the computed bretylium clearance during dialysis, but the fraction of the total body load eliminated during the same period was not proportionally significant. The strong linear relationships between renal and total clearance, β, and the creatinine clearance, may be helpful in adjusting dosage regimens for bretylium in patients with renal dysfunction. Clinical Pharmacology and Therapeutics (1983) 33, 144–150; doi: 10.1038/clpt.1983.22