Abstract

The metabolism and elimination of pyrilamine (2-[(2-dimethylamino-ethyl)(p-methoxybenzyl)amino]pyridine) were characterized after the iv administration of 7.0 mg/kg or 0.7 mg/kg pyrilamine maleate plus [14C]pyrilamine maleate to adult male Fischer-344 rats. Approximately 29% and 38% of the administered dose was excreted in the urine in the first 24 hr in the high and low dose groups, respectively, as determined by liquid scintillation spectrometry. Fecal excretion accounted for 27% and 30% of the administered dose in the first 24 hr in the high and low dose groups, respectively, as confirmed via combustion analysis. The 24-hr urinary metabolic products consisted of one major and four minor radiolabeled compounds. The major metabolite was isolated by reversed-phase high performance liquid chromatography and identified as the O-glucuronic acid conjugate of O-demethyl pyrilamine. This was accomplished by comparison of the chromatographic characteristics of this metabolite's aglycon with that of an authentic standard of O-demethyl pyrilamine and fast atom bombardment mass spectrometry of the unhydrolyzed conjugate. Pyrilamine and its N-oxide and O-demethyl derivatives were also identified after isolation by reversed-phase high performance liquid chromatography and comparison of their mass spectral and/or chromatographic properties with those of authentic compounds. The plasma metabolic profile was essentially the same as the urinary profile except for the absence of O-demethyl pyrilamine. The plasma elimination of pyrilamine fit a one-compartment open model and was first order. The terminal plasma elimination half-life of pyrilamine did not increase with increasing doses (2.3 hr, 0.7 mg/kg; 1.5 hr, 7.0 mg/kg) and thus pyrilamine does not exhibit dose-dependent elimination.(ABSTRACT TRUNCATED AT 250 WORDS)