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  • Title: Pharmacokinetics and metabolism of torasemide in man.
    Author: Neugebauer G, Besenfelder E, von Möllendorff E.
    Journal: Arzneimittelforschung; 1988 Jan; 38(1A):164-6. PubMed ID: 3370063.
    Abstract:
    Torasemide (1-isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3- sulfonyl)urea) is a potent new loop diuretic. The pharmacokinetics, absolute bioavailability and metabolic disposition of torasemide have been studied after administration of a standard-release tablet to healthy volunteers. According to a latin square design 9 subjects received in random order single doses of either 20 mg i.v. over 1 h or 20 or 40 mg p.o. On each of the three occasions, torasemide and its metabolites were analysed in plasma and urine up to 24 h. From the results of urinary excretion and plasma AUC, the availability of torasemide from the tablet was 80% to 90%, i.e. nearly complete. The kinetics were linear with dose. The time of peak was reached at 1 h, the elimination half-life varied from 3 h to 4 h. None of the metabolites M1, M3 or M5 found in plasma exhibited a longer half-life. Only a quarter of the low systemic clearance of torasemide (41 ml/min) was accounted for by renal clearance. The distribution volume of 15.5 l was in the order of the extracellular fluid volume. The total amount of torasemide and metabolites recovered in urine was 83%, i.e. 25% torasemide, 11% M1, 3% M3 (both active), and 44% M5 (inactive). Therefore, M1 and M3 probably contribute to the diuretic action of torasemide. Since the renal clearances of the metabolites exceeded that of the parent drug, renal impairment may change their elimination kinetics.
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