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PubMedDate not supplied

Oral torsemide in patients with chronic congestive heart failure: effects on body weight, edema, and electrolyte excretion. Torsemide Investigators Group.

STUDY OBJECTIVE: To assess the effects of torsemide on the primary end point of change in body weight from baseline, and the following secondary end points: urinary sodium, potassium, and chloride excretion, and urine volume after the first dose of drug. DESIGN: Randomized, parallel, double-blind, multicenter study in patients treated with torsemide 5 mg (n = 19), 10 mg (n = 18), or 20 mg (n = 14), or placebo (n = 15) for 7 days. PATIENTS: Sixty-six patients with New York Heart Association class II or III congestive heart failure and edema. RESULTS: At the end of the study, patients treated with torsemide 10 and 20 mg demonstrated a significant reduction in body weight compared with those receiving placebo (-1.62 and -1.30 kg, respectively), and those treated with torsemide 5 mg did not (-0.60 kg). The severity of edema decreased with increasing torsemide dose. Torsemide caused no greater frequency of adverse effects with increasing dose. CONCLUSION: Orally administered torsemide 5, 10, and 20 mg once/day for 7 days were well tolerated. Doses of 10 and 20 mg were effective in producing weight loss.

Administration, Oral↗

PubMedDate not supplied

Six-week study of torsemide in patients with congestive heart failure.

A double-blind, randomized, multicenter study compared treatment with 10 mg torsemide, 20 mg torsemide, and 40 mg furosemide, once daily, in 70 patients with congestive heart failure who had been maintained on 40 mg furosemide daily for at least 2 weeks. All three treatment groups showed statistically significant decreases in body weight, ranging from 1 to 3 kg at week 6. The decreases in body weight were significantly greater in the 20-mg torsemide group than in the furosemide group at weeks 4 and 6 and in the 10-mg torsemide group than in the furosemide group at week 4. The 20-mg torsemide group showed a statistically significant reduction in edema. Both the 10-mg and 20-mg torsemide groups showed statistically significant improvement in heart size. Pulmonary congestion decreased with treatment in each group. At week 6, both edema and pulmonary congestion were significantly less in the 20-mg torsemide group than in the 10-mg torsemide or 40-mg furosemide groups. Torsemide was well tolerated. Small, clinically insignificant decreases in serum potassium and increases in creatinine and uric acid were observed with both torsemide and furosemide. In conclusion, 20 mg torsemide was more effective than 40 mg furosemide in reducing body weight and improving symptoms of congestive heart failure.

Adult↗

PubMed1999

A pharmacoeconomic assessment of torsemide and furosemide in the treatment of patients with congestive heart failure.

The management of patients with congestive heart failure (CHF) can place a significant economic burden on managed care organizations, leading providers to seek treatments that are cost-effective. Diuretics play a significant role in the treatment of edema associated with CHF. We evaluated the use of 2 loop diuretics, torsemide and furosemide, in patients with CHF in a managed care setting. This prospective study compared clinical, economic, and quality-of-life outcomes in 240 patients randomized to the 2 drugs. Patients with New York Heart Association (NYHA) class II or class III CHF requiring loop diuretic treatment, either alone or in conjunction with other therapy, were eligible. Patients were told about the study during an office visit, and those with an interest in participating and who met the eligibility criteria were given further information and the opportunity to participate. After investigators obtained informed consent, patients were enrolled, randomized to either treatment, and followed for 6 months. Outcomes included CHF/cardiovascular (CV)-related medical costs, change in NYHA class, change in sodium retention score, hospitalizations, physician visits, medication use, adverse events, and change in quality of life. A total of 103 patients were randomized to torsemide, and 137 patients were randomized to furosemide. Except for body weight, patient demographic characteristics did not differ between groups at baseline; patients in the torsemide group were significantly heavier (P = 0.004). The results showed that mean total CHF/CV-related medical costs did not differ between groups (torsemide, $1520.07; furosemide, $1503.26; P = 0.975), despite higher mean drug-acquisition costs for torsemide patients ($121.01 vs $42.95; P < 0.0001). Mean costs were similar for CHF/CV-related hospitalizations (torsemide, $845.84; furosemide, $893.33; P = 0.918) and CHF-related physician visits (torsemide, $138.80; furosemide, $164.09; P = 0.288). Quality of life was significantly better for patients in the torsemide group at month 4 (P = 0.017), but not at month 2 (P = 0.059) or month 6 (P = 0.269). The number of adverse events did not differ significantly between groups (torsemide, 221; furosemide, 287; P = 0.916). The results of this study appear to indicate that in a representative cross-section of managed care patients, those who received torsemide, despite higher drug-acquisition costs, had similar CHF/CV-related management costs compared with furosemide recipients.

Aged↗

PubMed2005

Torsemide versus furosemide after continuous renal replacement therapy due to acute renal failure in cardiac surgery patients.

Diuretic therapy in ARF (acute renal failure) is mainly done with loop diuretics, first of all furosemide. Torsemide has a longer duration of action and does not accumulate in renal failure. In chronic and acute renal failure, both diuretics have been effectively applied, with a more pronounced diuretic effect for torsemide. In this study, the effects of torsemide versus furosemide on renal function in cardiac surgery patients recovering from ARF after continuous renal replacement therapy (CRRT) were studied. Twenty-nine critically ill patients admitted to an intensive care unit at a university teaching hospital after cardiac surgery recovering from ARF after CRRT were included in this prospective, controlled, single-center, open-labeled, randomized clinical trial. Inclusion criteria were urine output >0.5 mL/kg/h over 6 h under CRRT. Torsemide and furosemide dosages were adjusted with the target urine output being 0.8-1.5 mL/kg/h. Hemodynamic data, urine output, volume balance, serum creatinine clearance, electrolytes, blood urea nitrogen, serum creatinine, renin, and aldosterone concentrations were measured. Fourteen patients were included in the furosemide group and 15 patients in the torsemide group. Dosages of 29 (0-160) mg torsemide and a dosage of 60 (0-240) mg furosemide were given every 6 h in each group, respectively. The dosage given at the end of the study decreased significantly in furosemide and torsemide treated patients. Urine output, 24 h balance, and serum creatinine clearance did not differ significantly between groups. Urine output decreased in both groups, mostly dose-dependent in the torsemide group. The intragroup comparison of the first time-interval after inclusion with the last time-interval showed a significant increase in serum creatinine and blood urea nitrogen in the furosemide group. Renin and aldosterone concentrations did not show significant differences. In conclusion, torsemide and furosemide were effective in increasing urine output. Torsemide might show a better dose-dependent diuretic effect in ARF patients after CRRT treatment. Serum creatinine and blood urea nitrogen elimination were less pronounced in the furosemide group.

Acute Kidney Injury↗

PubMed1995

Torsemide: a pyridine-sulfonylurea loop diuretic.

OBJECTIVE: To review the clinical pharmacology of torsemide and to compare it with currently available loop diuretics, particularly furosemide. DATA SOURCES: An English-language MEDLINE search, 1985 to October 1994, was used to identify pertinent literature, including review articles. DATA EXTRACTION: Data from scientific literature were extracted, evaluated, and summarized for presentation. Pivotal and representative studies are discussed relating to the pharmacology, pharmacokinetics, and use of torsemide in patients with congestive heart failure, renal disease, hepatic disease, and hypertension. DATA SYNTHESIS: Torsemide is a loop diuretic of the pyridine-sulfonylurea class. The bioavailability of torsemide is approximately 80%, with little first-pass metabolism, and torsemide can be given without regard to meals. The serum concentration reaches its peak within 1 hour after oral administration and diuresis lasts approximately 6-8 hours. Torsemide is eliminated both hepatically (80%) and renally (20%) as unchanged drug with an elimination half-life of about 3.5 hours. Because of the high bioavailability, oral and intravenous doses are therapeutically equivalent. Torsemide, and other loop diuretics such as furosemide, are indicated for the treatment of edema associated with congestive heart failure, renal disease, and hepatic disease. They also are indicated for the treatment of hypertension alone or in combination with other antihypertensive agents. Depending on the indication, the recommended initial adult dosage of torsemide is between 5 and 20 mg once daily orally or intravenously. Special dosage adjustments in the elderly are not necessary. CONCLUSIONS: Torsemide is a loop diuretic similar to furosemide, with similar indications. Torsemide is characterized by good bioavailability and once-daily dosing and, compared with furosemide, provides generally equivalent therapeutic efficacy.

Clinical Trials as Topic↗

PubMed1996

Pharmacodynamics of torsemide administered as an intravenous injection and as a continuous infusion to patients with congestive heart failure.

The natriuretic and diuretic effects of a 100-mg dose of torsemide administered as a continuous infusion of torsemide and as a single bolus were compared in a group of patients with stable mild-to-moderate congestive heart failure (CHF). Patients received in random order 100 mg of torsemide as an intravenous bolus and as a 75-mg infusion over 24 hours started simultaneously with a 25-mg loading bolus. Administration of torsemide to patients with CHF as a continuous infusion was an effective dosing regimen, resulting in 24-hour diuresis and natriuresis that was numerically but not statistically greater than that observed with bolus administration. The response with continuous infusion occurred with less torsemide in the urine, resulting in a significantly greater efficiency of torsemide with this regimen. The effectiveness of torsemide as a continuous infusion does not mean that this mode of administration should be used in all patients. The response to 100 mg of torsemide in patients with mild-to-moderate CHF is the same whether administered as an intravenous bolus, a continuous intravenous infusion, or by mouth. This is consistent with the high bioavailability demonstrated in previous studies. The mode of therapy used should be dictated by each individual patient's needs. This study shows that continuous infusion is a viable option for administration of torsemide, and dosing guidelines for use of such a strategy are presented.

Adult↗

PubMed2004

CYP2C9 polymorphisms and the interindividual variability in pharmacokinetics and pharmacodynamics of the loop diuretic drug torsemide.

INTRODUCTION: According to in vitro data, torsemide (INN, torasemide) is a substrate of the genetically polymorphic enzyme cytochrome P450 (CYP) 2C9, but the impact of CYP2C9 polymorphisms on torsemide pharmacokinetics and pharmacodynamics has not been studied in humans. METHODS: A total of 36 healthy volunteers (12, 9, 1, 9, 3, and 2 carriers of CYP2C9 genotypes *1/*1 , *1/*2 , *2/*2 , *1/*3 , *2/*3 , and *3/*3 , respectively) received a single oral dose of 10 mg torsemide for pharmacokinetic and pharmacodynamic analysis. The effects of the CYP2C9 polymorphism on torsemide-induced urine volume and urinary elimination of sodium, potassium, chloride, and uric acid were measured during a salt-restricted diet. RESULTS: Median torsemide total oral clearance values were 3.4, 2.2, and 1.2 L/h in carriers of the CYP2C9 genotypes *1/*1 , *1/*3 , and *3/*3 , respectively, but there was no significant difference related to CYP2C9*2 . Values for metabolite formation clearance via metabolites M1 and M5 were 1.4, 1.7, 1.4, 1.0, 0.77, and 0.18 L/h in carriers of genotypes *1/*1 , *1/*2 , *2/*2 , *1/*3 , *2/*3 , and *3/*3 , respectively (P < .001). From 0 to 8 hours after torsemide administration, Na + , K + , and Cl - elimination was higher in carriers of CYP2C9*3 alleles than in carriers of the homozygous wild-type genotype, and 24-hour uric acid elimination values in urine were 451, 350, and 249 mg in carriers of 0, 1, and 2 CYP2C9*3 alleles, respectively (P = .003). CONCLUSION: Torsemide pharmacokinetics differed significantly between subgroups with different CYP2C9 genotypes, and diuretic effects were slightly more exaggerated in carriers of CYP2C9*3 alleles. To answer the question of whether these findings have clinical implications, further studies in patients undergoing long-term torsemide treatment are required.

Adult↗

PubMed1998

The effects of diuresis on the pharmacokinetics of the loop diuretics furosemide and torsemide in patients with heart failure.

PURPOSE: To evaluate the pharmacokinetics of furosemide and torsemide before and after diuresis in patients presenting with marked fluid overload. SUBJECTS AND METHODS: We studied 44 patients with New York Heart Association class III or IV heart failure, ejection fraction < or =40%, and an estimated excess fluid body weight > or =6.8 kg. Oral furosemide or torsemide was administered before and after diuresis. Pharmacokinetic parameters were assessed before and after diuresis. RESULTS: Following diuresis, maximum plasma concentration increased from 11.0+/-5.0 microg/mL to 13.9+/-6.8 with torsemide (P <0.05) and from 3.1< or =1.5 to 3.9+/-1.9 with furosemide (P=0.16). Maximum concentration increased by more than 30% in only one third of the patients. Total absorption (by area under the curve method) increased 6% among patients on torsemide (P=0.38) and 7% among patients on furosemide (P=0.63) and increased >30% in only 1 torsemide and 2 furosemide patients. The time to maximum concentration decreased from 1.40+/-.82 h to 0.81+/-0.36 with torsemide (P <0.01). There were no differences between furosemide and torsemide in the effects of edema on absorption. CONCLUSION: Marked diuresis altered the pharmacokinetics of both furosemide and torsemide in only a small percentage of patients. The use of adequate doses of oral diuretics in edematous patients may be successful, thereby permitting home treatment with oral diuretics and avoiding the cost of hospitalizations or home intravenous administration services.

Aged↗

PubMed2001

Long-term efficacy of torsemide compared with frusemide in cirrhotic patients with ascites.

BACKGROUND: Torsemide is a new loop diuretic that has shown, in short-term studies, to induce a longer and higher diuretic and natriuretic action than frusemide. However, torsemide long-term effects and complications have not been sufficiently investigated. The aim was to compare the efficacy and safety of torsemide versus frusemide in cirrhotic patients with uncomplicated ascites. METHODS: Forty-six patients were randomized in two groups to receive torsemide 20 mg/day (n = 22) or frusemide 40 mg/day (n = 24). Both drugs were administered in association with spironolactone 200 mg/day. The initial doses of diuretics were increased every 3 days up to 60, 120 and 400 mg/day, respectively, if the body weight loss was less than 300 g/day or natriuresis was below 50 mEq/day. RESULTS: Torsemide induced a significantly greater diuretic response than frusemide at 24 h and the maximum diuresis while mean diuresis was similar in both groups. Natriuresis was also higher with torsemide but the difference was not significant. The body weight loss, the treatment period, the ascites resolution and complications were similar in both groups. Diuretic doses were increased in two patients treated with torsemide and in nine patients treated with frusemide (P < 0.05). CONCLUSIONS: These results show that torsemide is as effective and safe as frusemide for long-term treatment of cirrhotic patients with ascites.

Adult↗

PubMed1995

Torsemide: a new loop diuretic.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of torsemide are reviewed. Torsemide belongs to the pyridine-sulfonylurea class of loop diuretics. Its primary site of activity is the thick ascending limb of the loop of Henle, where it blocks active reabsorption of sodium and chloride, resulting in diuresis, natriuresis, and other effects. Torsemide has high bioavailability, a relatively long half-life, and a prolonged duration of activity. It is highly protein bound. Clinical trials indicate that torsemide is effective in the treatment of hypertension and of edema and other symptoms in patients with chronic renal failure (CRF), hepatic dysfunction, or congestive heart failure (CHF). Torsemide has infrequent, mild, and transient adverse effects; among the most common are orthostatic hypotension, fatigue, dizziness, and nervousness. The recommended initial oral dosages of torsemide are 10-20 mg/day for CHF, 20 mg/day for CRF, 5 mg/day for hypertension, and 5-10 mg/day (in combination with a potassium-sparing diuretic or aldosterone antagonist) for hepatic cirrhosis. In most patients, the pharmacokinetic advantages of torsemide over other loop diuretics are unlikely to translate into a substantial edge in clinical outcomes, and in practice there may be no cost advantages. Although torsemide does not offer major advantages over other loop diuretics, it may be of benefit in patients who do not respond to or cannot tolerate other agents.

Antihypertensive Agents↗

PubMed2006

Torsemide renal clearance and genetic variation in luminal and basolateral organic anion transporters.

AIMS: To investigate the association between torsemide renal clearance and genetic variation in the basolaterally expressed renal organic anion transporters OAT1 and OAT3 and in the luminally situated OAT4. METHODS: We analysed 22 polymorphisms in the OAT coding genes SLC22A6, SLC22A8 and SLC22A11 and their haplotypes and measured torsemide renal clearance in 95 healthy men. In addition, the effect of torsemide on the OAT-mediated transport was studied in vitro. RESULTS: In stably transfected HEK293 cells torsemide (100 microm) inhibited the uptake by human OAT1, OAT3 and OAT4 by 63.1, 58.1 and 68.0%, respectively. Torsemide renal clearance ranged from 6.5 to 43.1 ml min(-1) with a log-normal distribution and a geometric mean of 15.6 ml min(-1) (15.0-16.1 +/- SEM). No clear outlier group was observed. AA carriers of the polymorphism rs11231809 in SLC22A11 had a torsemide renal clearance of 13.3 ml min(-1) (12.7-13.9) compared with 15.1 ml min(-1) (14.5-15.8) in AT and 18.0 ml min(-1) (16.7-19.5) in TT carriers (P = 0.002). The two most frequent haplotypes at SLC22A11 showed an association with torsemide renal clearance. Homozygous carriage of these two haplotypes resulted in renal clearances of 21.2 ml min(-1) (19.0-23.7) and 11.8 ml min(-1) (10.5-13.5), respectively. No association between reanl clearance and genetic variation in SLC22A6 or SLC22A8 was observed. CONCLUSIONS: Genetic variation in the gene encoding the luminally expressed OAT4 rather than in the basolaterally expressed OATs may affect the renal clearance of torsemide.

Adult↗

PubMed1996

Long-Term Treatment with Oral Torsemide and Its Effect on Body Weight and Fluid Balance in Patients with Chronic Renal Insufficiency.

Long-term treatment with oral torsemide was studied to determine its effectiveness in maintaining steady-state fluid balance in patients with chronic renal insufficiency by using a placebo-controlled, double-blind, random-off design. Patients with stable chronic renal insufficiency were initially titrated and then stabilized on torsemide. Once stabilized on torsemide, patients were randomly assigned in a double-blind fashion to continue on their titrated dose of torsemide or to receive a placebo. Of the 82 patients enrolled in the study, 68 were randomized to torsemide (n = 34) or placebo (n = 34). Patients who received the placebo showed a significantly greater (p < 0.001) mean increase in body weight (3.55 lb) than did patients who remained on torsemide (0.46 lb). Approximately two-thirds of the weight gain observed in the placebo group occurred during the first 3 days after randomization. Patients continued to receive treatment unless they developed fluid accumulation that was considered deleterious to their clinical state as determined by the investigator. In the placebo group a greater number of patients discontinued treatment because of weight gain or fluid accumulation. The mean number of days on treatment after randomization was significantly higher (p < 0.001) for patients who received torsemide (26 days) than for patients who received the placebo (16 days). The lack of weight gain in the torsemide group was associated with a higher percentage of patients who showed no change or an improvement in peripheral edema status (79%) than in placebo patients (35%). No patient was withdrawn from the study because of hyperkalemia or hypokalemia. The adverse effects reported during the study were as anticipated for patients with chronic renal insufficiency that is often complicated by other underlying illnesses.

Journal Article↗

PubMed1998

Pharmacokinetics of torsemide in patients with decompensated and compensated congestive heart failure.

Plasma pharmacokinetics of oral furosemide have been shown to be influenced by degree of decompensation in patients with congestive heart failure (CHF). This open-label, sequential comparison trial was conducted to determine whether CHF decompensation also alters the pharmacokinetics and pharmacodynamics of torsemide. Twelve patients with CHF, defined by either hemodynamic parameters or clinical signs and symptoms, were enrolled. On admission for treatment of their CHF, the patients were given 100 mg oral torsemide (phase A). A second dose of oral torsemide 100 mg was administered after hemodynamic parameters and clinical signs and symptoms of decompensated CHF resolved (phase B). Plasma and urine samples were collected over a 24-hour period for determination of torsemide concentrations and urine sodium. Hemodynamic measurements and physical signs and symptoms also were evaluated. During phase A, patients had significantly greater urine output and fractional sodium excretion compared with phase B. A significant increase in the area under the plasma concentration-time curve (AUC) was observed during phase B compared with phase A. However, no significant differences in maximal excretion rate of torsemide were noted between phase A and phase B. Heart failure status slightly affects the plasma pharmacokinetics of torsemide; however, this does not significantly alter the maximal urinary excretion rate of torsemide.

Area Under Curve↗

PubMed2001

Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure.

PURPOSE: Because the bioavailability of oral furosemide is erratic and often incomplete, we tested the hypothesis that patients with heart failure who were treated with torsemide, a predictably absorbed diuretic, would have more favorable clinical outcomes than would those treated with furosemide. PATIENTS AND METHODS: We conducted an open-label trial of 234 patients with chronic heart failure (mean [+/- SD] age, 64 +/- 11 years) from an urban public health care system. Patients received oral torsemide (n = 113) or furosemide (n = 121) for 1 year. The primary endpoint was readmission to the hospital for heart failure. Secondary endpoints included readmission for all cardiovascular causes and for all causes, numbers of hospital days, and health-related quality of life. RESULTS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to need readmission for heart failure (39 [32%] vs. 19 [17%], P <0.01) or for all cardiovascular causes (71 [59%] vs. 50 [44%], P = 0.03). There was no difference in the rate of admissions for all causes (92 [76%] vs. 80 [71%], P = 0.36). Patients treated with torsemide had significantly fewer hospital days for heart failure (106 vs. 296 days, P = 0.02). Improvements in dyspnea and fatigue scores from baseline were greater among patients treated with torsemide, but the differences were statistically significant only for fatigue scores at months 2, 8, and 12. CONCLUSIONS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to be readmitted for heart failure and for all cardiovascular causes, and were less fatigued. If our results are confirmed by blinded trials, torsemide may be the preferred loop diuretic for patients with chronic heart failure.

Aged↗

PubMed1995

Human hepatic cytochrome P450 2C9 catalyzes the rate-limiting pathway of torsemide metabolism.

Tolyl methylhydroxylation is the rate-limiting step in the elimination of torsemide, a newly developed diuretic, in humans in vivo. Kinetic and inhibitor studies with human liver microsomes and complementary DNA-expressed enzyme were performed to identify the cytochrome P450 (CYP) isoform responsible for torsemide tolyl methylhydroxylation to predict factors that might alter clearance in patients receiving torsemide. As in vivo, tolyl methylhydroxylation was the major biotransformation pathway in human liver microsomes. Microsomal tolyl methyl-hydroxylation kinetics followed Michaelis-Menten kinetics, with the mean apparent Km for the reaction being 11.2 +/- 1.3 microM. The microsomal reaction was almost completely abolished by the specific CYP2C9 inhibitor sulfaphenazole and was inhibited competitively by the alternative CYP2C9 substrate tolbutamide. Torsemide tolyl methylhydroxylase activity in microsomes from 16 human livers correlated significantly (rs = .81-.88) with tolbutamide and phenytoin hydroxylation, both CYP2C9-mediated reactions. Complementary DNA-expressed CYP2C9 catalyzed torsemide tolyl methylhydroxylation with an apparent Km (23 microM) similar to that observed for human liver microsomes and the IC50 values for sulfaphenazole inhibition of the reaction were essentially identical for the two enzyme sources. Taken together, these data demonstrate that human hepatic torsemide tolyl methylhydroxylation is catalyzed predominantly, if not solely, by CYP2C9. The implications of this finding for the regulation of torsemide metabolism in vivo are discussed.

Aryl Hydrocarbon Hydroxylases↗

PubMed1994

Intravenous torsemide as adjunctive therapy in patients with acute pulmonary edema.

The safety and efficacy of intravenous (i.v.) torsemide as adjunctive therapy for acute cardiogenic pulmonary edema was evaluated. Thirteen patients were treated with i.v. torsemide and six patients, with i.v. furosemide, as a positive control. Doses of torsemide, 20 mg or 40 mg, and furosemide, 40 mg or 80 mg, were administered initially. The dose was titrated as necessary over the next 24 hours. In patients who received i.v. torsemide, median fractional sodium excretion significantly increased from 2.88% (0.04-10.1%) at baseline to 6.76% (0.71-11.6%) at peak (P = 0.0342). Hourly urine volume increased from 134 mL (25-400 mL) to 375 mL (145-790 mL) (P = 0.0034). Torsemide administration resulted in a significant improvement in both pulmonary rales and orthopnea. None of the patients experienced serious adverse events or required withdrawal from the study. These results suggest that i.v. torsemide is an effective and well-tolerated diuretic in patients with acute cardiogenic pulmonary edema.

Acute Disease↗

PubMed1994

The pharmacokinetics of intravenous and oral torsemide in patients with chronic renal insufficiency.

Torsemide is a diuretic that acts in the thick ascending limb of the loop of Henle. Unlike furosemide, it undergoes substantial hepatic elimination and should not accumulate in patients with renal insufficiency. Therefore the pharmacokinetics of intravenous and oral torsemide and its metabolites were investigated in patients with chronic renal insufficiency. Two groups of 24 patients stratified by creatinine clearance (30 to 60 ml/min and < 30 ml/min) were studied in two separate randomized dose escalating crossover studies, one using intravenous torsemide and the other using oral torsemide. The pharmacokinetics of both intravenous and oral torsemide were linear over the dosage range studied. Absolute bioavailability was essentially 100%. Renal clearance was greatly diminished and correlated with renal function. Total plasma clearance and half-life were not related to renal function and were found to be similar to those of healthy subjects. The substantial nonrenal clearance of torsemide prevents accumulation in patients with chronic renal insufficiency.

Administration, Oral↗

PubMed1994

Dose-response study of intravenous torsemide in congestive heart failure.

In a double-blind dose-response study, 49 patients with New York Heart Association functional class III or IV heart failure were randomized to receive a single intravenous dose of 5, 10, or 20 mg torsemide or 40 mg furosemide. Torsemide produced dose-related decreases in body weight and increases in sodium and chloride excretion and urine volume. With the 20 mg dose of torsemide and the 40 mg dose of furosemide, body weight decreased significantly relative to baseline, and total and fractional 24-hour urinary excretion of sodium, chloride, and potassium and urine volume increased significantly. The 10 mg torsemide dose also produced a significant increase in urine volume. The results indicate that intravenous torsemide is effective for the acute treatment of sodium and fluid retention resulting from moderate to severe congestive heart failure.

Adult↗