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Effect of cigarette smoking on mexiletine kinetics
Author(s) -
GrechBélanger Odette,
Gilbert Marcel,
Turgeon Jacques,
LeBlanc PierrePaul
Publication year - 1985
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.1985.103
Subject(s) - mexiletine , kinetics , medicine , pharmacology , chemistry , anesthesia , physics , quantum mechanics
The effect of cigarette smoking on the kinetics of a single, 200 mg, oral dose of the antiarrhythmic drug mexiletine was investigated in healthy subjects. Cigarette smoking had no effect on absorption or distribution of the drug, but it significantly reduced the elimination t½ from 11.1 ± 3.4 to 7.2 ±1.8 hours; the effect on clearance was less significant. Determination of the urinary concentrations of the three major metabolites of mexiletine (mexiletine glucuronide conjugate, hydroxymethylmexiletine, and p ‐hydroxymexiletine) indicated that cigarette smoking selectively induced conjugation of mexiletine with glucuronic acid as well as aliphatic hydroxylation to yield hydroxymethylmexiletine, but that it had no effect on the formation of p ‐hydroxymexiletine. Clinical Pharmacology and Therapeutics (1985) 37 , 638–643; doi: 10.1038/clpt.1985.103