Studies on the metabolism of tripamide, a new antihypertensive agent.: I. Characterization of metabolites in rats

Abstract

1. Tripamide (N-(4-aza-endo-tricyclo [5.2.1.0^2,6]decan-4-yl)-4-chloro-3-sulphamoyl [carbonyl-¹⁴C]benzamide) was metabolized in rat to yield five metabolites which were separated by chromatography, and characterized by mass spectrometry and reverse isotope dilution analysis.

2. The five metabolites were identified as follows; N-(3(or 5)- hydroxy-4-aza-endo-tricyclo[5.2.1.0^2.6]decan-4-yl)-4-chloro- 3-sulphamoylbenzamide (3-hydroxy-tripamide); N-8(or 9)-hydroxy-4- aza-endo-tricyclo[5.2.1.0^2.6]decan-4-yl)-4-chloro-3- sulphamoylbenz-amide (8-hydroxy-tripamide); 4-chloro-3-sulphamoylbenzamide; 4-chloro-3-sulphamoyl-benzoic acid; and 4-chloro-3-sulphamoylbenzoic acid-(N′-acetyl)hydrazide.

3. Tripamide was metabolized rapidly and the major metabolite was 4-chloro-3-sulphamoylbenzoic acid in rat blood.

4. After intravenous injection, the excretion rate of the hydroxylated tripamide into bile was about 2-3 times faster than that into urine.