Drug-nitrite interactions: the lack of toxicity of a N-nitroso derivative of tripelennamine formed in the rat.

[Benzyl-¹⁴C]-tripelennamine (100 mg/kg, 100 μCi/kg) and sodium nitrite (100 mg/kg) were administered orally to 24-hr fasted rats. After 1 hr, the rats were sacrificed and the stomach contents were analyzed for the N-nitroso derivative of tripelennamine with the aid of preparative thin-layer chromatography (tlc) and mass spectrometry. About 6% conversion of the administered drug to its N-nitroso derivative was found to occur in the rat stomach during the first hour. The N-nitroso compound was also detected in the 24- and 48-hr urine samples from rats to which tripelennamine and nitrite were coadministered. The N-nitroso derivative failed to produce any definitive hepatic or kidney necrosis in rats during acute and short-term toxicity studies, and it was found to be devoid of the central nervous system (CNS) activity of the parent drug.