CLINICAL PHARMACOKINETICS AND PHARMACODYNAMICS OF TORASEMIDE

The new loop diuretic torasemide belongs to the pyridine sulfonylurea class. It is well absorbed and yields a bioavailablity of about 80% in healthy individuals, even higher in patients with oedema. This is rou ghly double that of the 'classical' loop diuretic furosemide (frusemid e) [26 to 65%]. Torasemide is highly bound to protein (99%) as is furo semide. The volume of distribution of torasemide was determined as 0.2 L/kg as compared with 0.11 to 0.18 L/kg for furosemide. Torasemide un dergoes extensive hepatic metabolism; only 20% of the parent drug is r ecovered unchanged in the urine. For comparison only 10 to 20% of furo semide undergoes phase II metabolisation (to the glucuronide). In chro nic renal failure the renal clearance of torasemide decreased in propo rtion to the decrease of the patients' glomerular filtration rate, whe reas the total plasma clearance (3 times that of the renal clearance) appeared to be independent of renal function. As expected, the renal e xcretion of torasemide metabolites is significantly retarded in renal disease. The pharmacokinetics of torasemide are significantly influenc ed by liver disease. Total plasma clearance of torasemide was reduced to about half of that found in the control group, yielding an increase in elimination half-life. A greater than normal fraction of torasemid e was recovered in the urine of patients with cirrhosis. In contrast, the kinetics of furosemide appeared to depend more on kidney function than on liver disease. The pharmacodynamics of torasemide are principa lly the fame as those reported from conventional loop diuretics due to their interference with one binding site in the thick ascending limb of Henle's loop, the Na+:K+:2Cl(-) carrier, The maximum natriuretic ef fect of all loop diuretics amounts to about 3 mmol Na+/min. Members of this class differ, however, with respect to their intravenous potency or affinity for the receptor, respectively: bumetanide > piretanide > torasemide > furosemide. So far, the only loop diuretic which has bee n shown to effectively lower high blood pressure is torasemide. This e ffect occurs at the low dose of 2.5 mg/day.