Effect of coadministration of procainamide and isoniazid on each other's acetylation pathway

The effect of isoniazid (INH) and procainamide (PA) on each other's acetylation pathway was studied in 7 normal subjects (3 rapid acetylators, 3 slow acetylators, 1 of indeterminate phenotype). Oral PA (6 mg/kg) was administered every 4 h for a total of seven doses. Following the final dose subjects received a single 300-mg oral dose of INH. Analysis of the parent drugs and their acetylated metabolites in plasma and urine revealed no effect on the acetylation of either drug. In 2 subjects (1 rapid, 1 slow acetylator) increasing doses of PA were given and the effect on INH (300 mg) acetylation measured. High mean circulating levels of PA (7.1 microgram/ml) appeared to inhibit acetylation of INH in the rapid acetylator whereas a mean PA plasma level of 8.6 microgram/ml had no effect on INH acetylation in the slow acetylator. However, the results from this study suggest that alterations of INH acetylation by PA are unlikely to be of clinical significance.