Site of action of torasemide in man

Cuvelier, R; Pellegrin, P.; Lesne, Michel; Strihou, Charles van Ypersele de

doi:10.1007/bf00541462

Cited by 15 publications

(2 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the pharmacokinetics and pharmacodynamics of torasemide after intravenous or oral administration to humans and animals [10,[12][13][14][15][16][17] have been investigated, it appears that no detailed studies on the effects of intravenous infusion time for the same total dose of torasemide on its pharmacokinetics and pharmacodynamics have been reported to date. This paper will report the results of such a study using rabbits as an animal model.…”

Section: Introductionmentioning

confidence: 99%

Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbits

Kim

Lee

et al. 2004

Biopharm & Drug Disp

View full text Add to dashboard Cite

The pharmacokinetics and pharmacodynamics of torasemide were evaluated after intravenous administration of the same total dose of torasemide at a dose of 1mg/kg to rabbits with different infusion times, 1 min (treatment I), 30 min (treatment II) and 2 h (treatment III). The loss of water and electrolytes in urine induced by torasemide was immediately replaced with infusion of an equal volume of lactated Ringer's solution. All the pharmacokinetic parameters of torasemide, such as total area under the plasma concentration-time curve from time zero to time infinity (AUC), total body clearance (CL), apparent volume of distribution at steady state (Vss), terminal half-life and mean residence time (MRT), were independent of infusion times. However, the 8 h urine output (235, 534 and 808 ml) and 8 h urinary excretion of sodium (24.2, 80.1 and 89.2 mmol) and chloride (27.1, 89.2 and 94.0 mmol) were significantly greater in treatments II and III than those in treatment I, although the total 8 h urinary excretion of unchanged torasemide (1210, 1210 and 1310 microg) were not significantly different among the three treatments. This could be due to the higher diuretic efficiencies in treatments II and III.

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbits

Kim

Lee

et al. 2004

Biopharm & Drug Disp

View full text Add to dashboard Cite

show abstract

“…It inhibits reversibly to Na + -K + -2 Cl À transport carrier system in the thick ascending limb of loop of Henle [6] like other loop diuretics. This main site of action, thick ascending limb of loop of Henle, has been determined in humans [7], in rats and dogs through clearance studies [8] and in rats through clearance and micropuncture techniques [9]. Hence, it inhibits water and solute reabsorption mainly in the thick ascending limb of loop of Henle.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of intravenous trasemide in mutant nagase aalbuminemic rats

Kim

Lee

2002

Biopharm & Drug Disp

View full text Add to dashboard Cite

The importance of plasma protein binding of intravenous furosemide in circulating blood for its urinary excretion and hence its diuretic effects in mutant Nagase analbuminemic rats (NARs, an animal model for human familial analbuminemia) was reported. Based on the furosemide report, the diuretic effects of another loop diuretic, torasemide, could be expected in NARs if plasma protein binding of torasemide is considerable in the rats. This was proven by this study. After intravenous administration of torasemide, 10 mg/kg, to NARs, the plasma protein binding of torasemide was 23.3% in the rats due to binding to alpha- and beta-globulins (this value, 23.3%, was greater than only 12% for furosemide), and hence the percentages of intravenous dose of torasemide excreted in 8-h urine as unchanged drug was 14.9% in the rat (this value was considerably greater than only 7% for furosemide). After intravenous administration of torasemide to NARs, the AUC (301 versus 2680 microg/min/ml) was significantly smaller [due to significantly faster both Cl(r) (4.81 versus 0.386 ml/min/kg) and Cl(nr) (28.3 versus 3.33 ml/min/kg)], terminal half-life (18.3 versus 73.5 min) and mean residence time (6.97 versus 61.8 min) were significantly shorter (due to faster Cl, 33.2 versus 3.74 ml/min/kg), and amount of 8-h urinary excretion of unchanged torasemide (446 versus 323 microg, due to increase in intrinsic renal excretion) was significantly greater than those in control rats. The 8-h urine output and 8-h urinary excretions of sodium and chloride were comparable between two groups of rats although the 8-h urinary excretion of torasemide was significantly greater in NARs. This could be explained by the following. The amount of urinary excretion of torasemide was significantly greater in NARs than that in control rats only between 0 and 30 min urine collection. In both groups of rats, the urinary excretion rate of torasemide during 0-30 min reached an upper plateau with respect to urine flow rate as well urinary excretion rates of sodium and chloride. Therefore, the diuretic effects (8-h urine output and 8-h urinary excretions of sodium and chloride) were not significantly different between the two groups of rats.

show abstract

Diuretic Treatment for the Sodium Retention of Congestive Heart Failure

Cody

Kubo²,

Pickworth³

1994

Arch Intern Med

View full text Add to dashboard Cite

The use of diuretics for the treatment of sodium retention in congestive heart failure was evaluated. Particular focus was given to the altered renal response to diuretics in patients with heart failure and adverse responses to diuretic therapy. Highlighted information included historical aspects of the development of diuretics, mechanisms of sodium retention, the physiologic and clinical response to diuretics, and the altered pharmacokinetics and pharmacodynamics of diuretics in congestive heart failure. Despite more than 60 years of empiric diuretic use in heart failure, the actual database regarding the long-term efficacy, adverse effects, and altered mortality outcome in heart failure is relatively small. Existent pharmacokinetic and pharmacodynamic data are typically not collected within the context of heart failure efficacy trials. In addition to altered electrolyte transport and total-body electrolyte depletion, diuretics may be associated with adverse neurohormonal activation. Thus, guidelines for acute and long-term therapy with diuretics in heart failure remain somewhat empiric. Diuretics will remain a mainstay for the treatment of edema in congestive heart failure but must be accompanied by moderate sodium restriction. However, large clinical trials of diuretics would be necessary to demonstrate that improved clinical efficacy with edema reduction is not offset by adverse effects, which include electrolyte depletion, ventricular arrhythmias, and subsequent increased mortality.

show abstract

Site of action of torasemide in man

Cited by 15 publications

References 5 publications

Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbits

Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbits

Pharmacokinetics and pharmacodynamics of intravenous trasemide in mutant nagase aalbuminemic rats

Diuretic Treatment for the Sodium Retention of Congestive Heart Failure

Contact Info

Product

Resources

About