The Acetylation of Isoniazid in Alcoholics

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Abstract
The rate of acetyl-ation of isoniazed, the inactivation of which is known to be under genetic control, was studied in 28 male alcoholics to test the hypothesis that a difference in acetate availability and rate of utilization exists between alcoholics and nonalcoholics. The isoniazed half-lives in the 28 alcoholics were estimated; their statistical distribution was bimodal. A division of the subjects into various drinking pattern types compared to the isoniazid phenotype was not revealing. To exclude the operation of other factors as the cause of the difference, experiments also were done with 2 nonalcoholics with disparate isoniazid inactivation rates (a half-life of 250 minutes in one and 110 minutes in the other). Results showed that plasma binding and deacetylase activity were not responsible for the difference, although renal clearance accounted for some of the difference. Maintenance of 0.02 to 0.04% alcohol in the blood prior to and during the determinations of the half-lives resulted in a 30% decrease in the half-lives in both subjects.

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