Chemical formula: C₁₆H₂₀N₄O₃S Molecular mass: 348.42 g/mol PubChem compound: 41781
Torasemide acts as a salidiuretic by inhibition of renal sodium and chloride reabsorption in the ascending limb of the loop of Henle.
Torasemide is a loop diuretic. However, at low doses its pharmacodynamic profile resembles that of the thiazide class regarding the level and duration of diuresis. At higher doses, torasemide induces a brisk diuresis in a dose dependant manner with a high ceiling of effect.
After oral administration the onset of diuresis is within the 1st hour with a peak action within 2 to 3h. The action may last up to 12h.
In healthy subjects an increase in dose results in a linear increase in urine excretion corresponding to the logarithm of the dose (high-ceiling activity) within the 5 to 100 mg dose range. An increase in diuresis may also take place if other diuretics are no longer active, eg in the presence of impaired renal function.
In renal failure endogenous organic acids compete with loop diuretics for the acid secretion mechanism in the proximal tubule. Therefore, the torasemide dose has to be adequately increased in otrder to achieve effective amounts of drug at the site of action.
Torasemide leads to a gentle removal of edema and especially to an improvement of the working condition of the heart failure by reducing the preload and afterload. In patients with severe to endstage chronic renal failure there is a reduction of aterial blood pressure in addition to removal of edema and maintenance of residual diuresis.
Torasemide is absorbed rapidly and almost completely after oral administration, and peak serum levels are reached after one to two hours.
More than 99% of torasemide is bound to plasma proteins.
The apparent distribution volume is 16 litres.
Torasemide is metabolised to three metabolites, M1, M3 and M5 by stepwise oxidation, hydroxylation or ring hydroxylation. Further metabolites (M2 and M4) have been found in animal experiments, but not in humans.
The terminal half-life of torasemide and its metabolites is three to four hours in healthy subjects. Total clearance of torasemide is 40ml/min and renal clearance about 10ml/min. About 80% of the dose administered is excreted as torasemide and metabolites into the renal tubule-torasemide 24%, M1 12%, M3 3%, M5 41%.
In patients with congestive heart failure and disorders of liver fnction, the elimination half-lives of torasemide and metabolite M5 are only slightly increased compared with those in healthy volunteers. The amounts of torasemide and metabolites excreted in the urine are similar to those in healthy subjects; therefore no accumulation is to be expected.
In the presence of renal failure, elimination half-life of torasemide is unchanged.
Very low toxicity.
The changes observed in toxicity studies in dogs and rats at high doses are attributable to an excess pharmacodynamic action (diuresis). Changes observed were weight reduction, increases in creatinine and urea and renal alterations such as tubular dilatation and interstitial nephritis. All drug induced changes were shown to be reversible.
Reproduction toxicology studies in the rat have shown no teratogenic effect, but malformed foetuses have been observed after high doses in pregnant rabbits. No effects on fertility have been seen.
Torasemide showed no mutagenic potential. Carcinogenicity studies in rats and mice showed no tumourigenic potential.
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