Pharmacological properties of the new potent diuretic torasemide in rats and dogs.
Torasemide, a pyridine-3-sulfonylurea derivative, has potent diuretic activity in rats and dogs. In both species urinary volume and electrolyte excretion increased linearly with the logarithm of the dose, thus resembling the profile of a high ceiling diuretic. The minimum effective dose by oral route was 0.2 mg/kg in the rat and less that 0.1 mg/kg in the dog. Maximal effect was obtained with about 10 mg/kg. Experiments by oral and i.v. routes in the rat indicated that torasemide was equally potent by both oral and parenteral administration. In both rats and dogs, urinary excretions induced by torasemide were similar to those obtained with furosemide. However, for the same natriuretic effect, potassium losses with torasemide were significantly less than with furosemide. On a weight basis, torasemide was 9-40 times more potent than furosemide in the rat and about 10 times in the dog. After oral administration the diuretic effects of torasemide started within 20 min and lasted approximately 2 h in the rat and more than 8 h in the dog. The activity of torasemide was not decreased after a repeated daily oral dose of 10 mg/kg for 15 days in the rat. Torasemide at a daily oral dose of 5 mg/kg for 12 days effectively reduced the arterial blood pressure in desoxycortone induced hypertension in the rat. Besides the diuretic and antihypertensive effects no other significant pharmacological effects were observed with torasemide in the different in vitro and in vivo experiments. Torasemide was practically fully absorbed by the gastrointestinal tract, its bioavailability by oral route ranged from 80 to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000959:Antihypertensive Agents; D001798:Blood Proteins / Q000378:metabolism; D002415:Cats; D003900:Desoxycorticosterone; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D004573:Electrolytes / Q000652:urine; D005665:Furosemide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013449:Sulfonamides / Q000494:pharmacology*; D014018:Tissue Distribution; D000077786:Torsemide
D000959:Antihypertensive Agents; D001798:Blood Proteins; D004232:Diuretics; D004573:Electrolytes; D013449:Sulfonamides; D003900:Desoxycorticosterone; D005665:Furosemide; D000077786:Torsemide