Pharmacokinetics and Pharmacodynamics of Torasemide in Health and Disease

Torasemide is a new loop diuretic that differs from others in this class in that only 20% of the drug is excreted unchanged in the urine with the remaining 80% being eliminated by hepatic metabolism. The large component of nonrenal clearance would predict that torasemide would have only minimal accumulation and prolongation of half-life in patients with renal insufficiency, and this proves to be the case. In contrast, in patients with liver disease, impairment of hepatic elimination causes accumulation of torasemide in plasma with prolongation of half-life. In addition, in cirrhosis, there is increased elimination of unchanged drug into the urine compared to healthy controls. In patients with renal insufficiency, response to remaining nephrons is normal as has been observed with other loop diuretics. In patients with cirrhosis and in those with congestive heart failure, response is diminished, again as has been observed with other loop diuretics. Interestingly, in patients with cirrhosis, the increased delivery of drug into the urine is sufficient to compensate for the decreased pharmacodynamics of response so that overall response is similar to that which occurs in health subjects.