Tripamide

Abstract: An inclusion compound composed of tripamide and cyclodextrin markedly improves the solubility of tripamide which is effective for treatment of essential hypertension.

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-sulphamoylbenzamide (8-hydroxy-tripamide); 4-chloro-3-sulphamoylbenzamide; 4-chloro-3-sulphamoylbenzoic 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.

Abstract: Tripamide is a drug widely used in clinical practice for the treatment of hypertension and edema This work evaluated a screening method for Tripamide and its urinary metabolites in human urine, using high-performance liquid chromatography diode-array detection (HPLC/DAD) Identification of these metabolites was investigated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) after dosing with 15 mg Tripamide Acid hydrolysis showed that Tripamide is conjugated in the body Two suspected metabolites were detected by HPLC/DAD HPLC/ESI-MS/MS analysis suggested that these metabolites were probably hydroxylated together with loss of the -NH(2) group and dehydrogenation These results will be useful in confirmation methods for Tripamide in doping control

Abstract: The effects of tripamide and hydrochlorothiazide on blood pressure and glucose tolerance were studied in 20 hypertensive patients, half of whom had type II diabetes mellitus. Each patient underwent intravenous glucose tolerance testing before and after 4 weeks of treatment with tripamide, 10 mg, and, at a separate time, hydrochlorothiazide, 50 mg. Both tripamide and hydrochlorothiazide lowered blood pressure; for both drugs, the magnitude of the reduction in mean arterial pressure was positively correlated with the pretreatment mean arterial pressure. Hydrochlorothiazide produced a greater fall in serum potassium than did tripamide. In the nondiabetics, neither drug produced a significant change in the glucose disappearance curve or the plasma insulin response. In the diabetics, hydrochlorothiazide produced an increase in serum glucose levels, but the plasma insulin response, which was blunted in comparison to the nondiabetics, did not change. Tripamide did not affect serum glucose or plasma insulin levels in either group of patients. Tripamide at a dose of 10 mg daily does not affect glucose tolerance in either nondiabetic hypertensive patients or patients with type II diabetes mellitus.