Effect of the immunomodulator tilorone on the in vivo acetylation of procainamide in the rat.

Interferon and interferon inducers have been found to inhibit cytochrome P-450-dependent metabolism in animals and man. The effect of these agents on the acetylation of drugs has not been previously reported. Since these agents stimulate the reticuloendothelial system, together with the abundance of N-acetyltransferase in the reticuloendothelial system, it was hypothesized that these immunomodulators may affect drug acetylation. To test this hypothesis, the effect of tilorone (a synthetic interferon inducer) on the in vivo acetylation of procainamide was examined in the rat. Pretreatment with tilorone hydrochloride (50 mg/kg) 48 hr prior to the administration of procainamide hydrochloride (50 mg/kg) resulted in a 32% increase in the urinary recovery of N-acetylprocainamide and a 35% increase in the metabolic clearance of procainamide to N-acetylprocainamide. These data indicate that interferon inducers increase the N-acetylation of drugs in vivo.