Disposition and metabolism of triprolidine in mice.

The disposition of the antihistamine, triprolidine, was studied in male and female CD-1 mice after a single oral 50 mg/kg dose of [14C]triprolidine HCl. Urine and feces collected over 72 hr postdosing were analyzed for total radiocarbon, and for parent drug and metabolites by radiochromatography. Structures of metabolites were determined by GC/MS, direct probe MS, FAB/MS, LC/MS, NMR, and IR techniques. More than 80% of the dose was recovered in the urine, with the remainder recovered in the feces. The carboxylic acid analog of triprolidine (219C69) was found to be the major metabolite in urine and feces, accounting for an average of 57.6% of the administered dose. Three minor metabolites were identified as a gamma-aminobutyric acid analog of triprolidine, a pyrrolidinone analog of 219C69, and a pyridine-ring hydroxylated derivative of triprolidine. Parent drug could only be detected in urine and accounted for 0.3% (females) to 1.1% (males) of the dose. The results of this study showed that triprolidine was absorbed well but extensively metabolized when administered orally to mice.