The effect of isoniazid and other drugs on the acetylation of procainamide in the intact rat.

The effects of isoniazid (INH), hydralazine, salicylazosulfapyridine, and sulfapyridine on the quantitative disposition of procainamide (PA) in the intact rat were examined. A dose-dependent inhibition of PA acetylation was observed after coadministration of PA with INH via nasogastric intubation. The 24-hr urinary excretion of N-acetylprocainamide was noted to decline in the presence of INH whereas that of the unchanged drug exhibited a coincident rise. A reduction in the systemic clearance of PA and a prolongation in its half-life of elimination was also observed. INH increased PA hepatic levels and decreased N-acetylprocainamide hepatic content. In contrast hydralazine affects not only PA acetylation but also its absorption rate and transformation by other metabolic pathways. Salicylazosulfapyridine did not affect PA acetylation whereas high doses of sulfaphridine did.