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Oral and intravenous bretylium disposition
Author(s) -
Anderson Jeffrey L,
Patterson Eugene,
Wagner John G,
Stewart James R,
Behm Harriet L,
Lucchesi Benedict R
Publication year - 1980
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.1980.190
Subject(s) - bretylium , chemistry , urine , oral administration , pharmacokinetics , pharmacology , volunteer , medicine , biochemistry , receptor , adrenergic , agronomy , biology
To compare the oral and intravenous disposition of bretylium tosylate in man, 10 normal male subjects were randomly assigned single doses of 5 mg/kg bretylium tosylate either orally or intravenously and crossed over 2 wk later to the opposite route (20 studies). Each experiment included sampling for drug in serum and urine over 48 hr. Bretylium tosylate was assayed by gas chromatography. Kinetic analysis provided the following mean [coefficient of variation] results: 100F Po , 22.6% [40.2%]; Cl IV r , 300 ml/min [27.8%]; Cl Po r , 1,268 mg/min [54.8%]; Cl IV B 299 ml/min [31.9%]; f, 101% [8.7%]; V dss , 3.37 l/kg [30.5%]; λ IV l , 0.0510 [12.8%]; λ PG l , 0.115 [52.7%] hr −1 ; elimination half‐life (t½) after intravenous bretylium tosylate, 13.6 hr, and after oral bretylium tosylate, 6.0 hr (harmonic means). Bretylium tosylate binding to plasma proteins in normal volunteer samples was found to be negligible. The results indicate extensive tissue binding of bretylium tosylate. Oral doses of bretylium tosylate are only partially absorbed. Bretylium tosylate is eliminated entirely by the kidneys as unchanged drug. The greater renal clearance after oral than intravenous bretylium tosylate, and the greater elimination rate constant and shorter oral bretylium tosylate t½ are of interest but no explanation is available. Clinical Pharmacology and Therapeutics (1980) 28, 468–478; doi: 10.1038/clpt.1980.190