Ranitidine does not impair oxidative or conjugative metabolism: Noninteraction with antipyrine, diazepam, and lorazepam

Abstract

Potential interactions of ranitidine [an antiulcer drug] with antipyrine, diazepam and lorazepam were evaluated. Ten healthy male subjects were injected i.v. with antipyrine (1.2 g), diazepam (10 mg), or lorazepam (2 mg) on 2 randomly assigned occasions, once in the otherwise drug-free state and once while concurrently taking a therapeutic ranitidine dose of 150 mg every 12 h. Kinetic analysis for antipyrine showed no change in elimination t1/2 [half-life] between trials (mean, 11.6 and 11.5 h) with no change in volume of distribution (Vd) or total clearance (0.77 and 0.75 ml/min per kg). Diazepam analysis also showed unchanged t1/2 (32.3 and 28.9 h) with no change in Vd or total clearance (0.42 and 0.39 ml/min per kg). Lorazepam also had unchanged t1/2 (11.7 and 11.3 h), Vd and total clearance (1.52 and 1.65 ml/min per kg). Ranitidine, unlike cimetidine, had no effect on either human hepatic drug oxidation, as measured by antipyrine and diazepam clearance, or human drug conjugation, as measured by lorazepam clearance.