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  • Title: Pharmacokinetics and pharmacodynamics of torasemide in congestive heart failure.
    Author: Kramer WG.
    Journal: Cardiology; 1994; 84 Suppl 2():108-14. PubMed ID: 7954532.
    Abstract:
    The pharmacokinetic profile and pharmacodynamic activities of torasemide, a new pyridine sulfonylurea acting on the loop of Henle, are described. Absorption of the drug was unchanged in patients with congestive heart failure, though maximum concentrations occurred at 1.7 h compared with 0.9 h in healthy subjects. The volume of distribution after oral administration was also unchanged in patients with heart failure, but oral clearance was reduced by 50%, consistent with the increase in elimination half-life; renal clearance and maximum urinary torasemide excretion rate were also reduced by 50%. Thus, the primary pharmacokinetic alteration in patients with heart failure compared with healthy subjects was a reduction in the rate of delivery of torasemide to its site of action in the loop of Henle. Fractional sodium excretion and urinary torasemide excretion rate were similar in patients with heart failure and healthy subjects, though the relationship between the excretion rates of sodium and torasemide was depressed in the patients with heart failure. Thus, the primary pharmacodynamic alteration in patients with heart failure compared with healthy subjects was less total sodium excretion per molecule of torasemide reaching the renal tubule. Torasemide was effective in inducing loss of body weight and increased sodium excretion in patients with congestive heart failure. Single intravenous and oral doses of 20 mg both produced similar significant increases in total sodium excretion. Torasemide, 5-20 mg once daily for up to 6 weeks, produced significant loss of body weight and increased total sodium excretion confirming the diuretic effectiveness of torasemide in patients with congestive heart failure.
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