托拉塞米与呋塞米治疗儿童肾病综合征伴高度水肿的疗效评价

目的:观察托拉塞米与呋塞米治疗儿童肾病综合征引起水肿的临床疗效。方法:选取54例儿童肾病综合征患儿,将54例患儿分为托拉塞米组、呋塞米加口服补钾组、呋塞米组各18例。三组患儿在激素及一般治疗的基础上,托拉塞米组给予静脉注射托拉塞米1 mg/(kg·d),每次不超过20 mg;呋塞米加口服补钾组给予静脉注射呋塞米2 mg/(kg·d),每次不超过40 mg,并口服补钾;呋塞米组给予静脉注射呋塞米2 mg/(kg·d),每次不超过40 mg。三组患儿分别于治疗前1 d、治疗后每天记录24 h尿量,治疗前及治疗后第4天抽外周血查电解质的变化情况,并记录不良反应。结果:三组患儿治疗后尿量较治疗前均显著增多,但治疗后前3 d平均尿量三组比较差异无统计学意义(P>0.05);呋塞米组治疗后第4天血钾浓度较其余两组降低明显(P<0.05);托拉塞米组和呋塞米加口服补钾组患儿治疗后第4天血钾浓度比较差异无统计学意义(P>0.05)。结论:临床上对于儿童肾病综合征引起的水肿应用托拉塞米或呋塞米治疗效果显著。应用呋塞米时同时口服补钾可减轻其致低血钾的不良反应。     

托拉塞米注射液治疗急性左心衰竭的临床分析

目的：观察分析托拉塞米注射液对急性左心衰竭的疗效及安全性。方法：将102例急性左心衰竭患者随机分为治疗组（51例）和对照组（51例）,治疗组应用托拉塞米注射液20～80mg,对照组应用呋塞米注射液20—100mg,其余治疗相同,观察两组疗效、血气分析及电解质等的变化,并记录不良反应。结果：治疗组有效率90．2％,对照组有效率86-3％,组间差异无统计学意义;治疗组和对照组治疗后氧分压提高显著,P〈0．05;治疗组较对照组钾离子变化较小,两组比较P〈0．05。结论：应用托拉塞米注射液治疗急性左心衰竭疗效显著,安全性好。     

托拉塞米和呋塞米治疗心肾综合征疗效对比观察

目的 比较托拉塞米和呋塞米治疗心肾综合征的疗效及安全性.方法 60例合并肾功能不全的心力衰竭患者入院肌酐水平Ⅰ级40例、Ⅱ级20例,均完全随机平均分成托拉塞米组和呋塞米组.在常规治疗基础上,托拉塞米组加用托拉塞米20 mg/d静脉注射,呋塞米组加用呋塞米40 mg/d静脉注射.给药前后测定患者血钾、血钠、血钙、肌酐水平,记录24h尿量,同时观察患者的症状、心功能变化及不良反应发生率.结果 不同入院肌酐水平(Ⅰ级和Ⅱ级)患者托拉塞米组日平均尿量均明显高于呋塞米组[( 1685±49)rnl比(1442±38) ml,( 1042±32) ml比(968±38)ml,P＜0.05].肌酐水平Ⅰ级患者托拉塞米组心功能好转率高于呋塞米组[75％ (15/20)比65％ (13/20)],且血钾较呋塞米组明显升高[(+0.03±0.01) mmol/L比(-0.01 ±0.01)mmol/L,P＜0.05],托拉塞米组血肌酐波动范围明显较小(P＜0.05).不同肌酐水平(Ⅰ级和Ⅱ级)2组水肿消退率比较差异无统计学意义(P＞0.05),肌酐水平Ⅱ级患者心功能好转率及血钾变化2组比较差异无统计学意义(P＞0.05).托拉塞米组不良反应发生率为6.7％ (2/30),呋塞米组不良反应发生率为30.0％(9/30),2组比较差异有统计学意义(P＜0.01).结论 对心肾综合征患者,托拉塞米利尿作用及对机体内环境的稳定性明显优于呋塞米.     

Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary hypertension secondary to heart failure through enhancing the natriuretic peptides-cGMP pathway

In advanced heart failure (HF), the compensatory pulmonary vasodilation is attenuated due to the relative insufficiency of cGMP despite increased secretion of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n = 7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270 bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP), cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared with the vehicle group despite low plasma ANP levels associated with improvement in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP levels in both groups, whereas it did not change all hemodynamic parameters in the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly increased pulmonary arterial pressure and pulmonary vascular resistance. These results indicated that long-term treatment with a PDE5 inhibitor improved pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to this therapeutic effect.     

Torasemide: a pharmacoeconomic review of its use in chronic heart failure.

Torasemide is a loop diuretic used for the treatment of hypertension and for oedema in chronic heart failure (CHF), renal failure and cirrhosis. The efficacy of torasemide in reducing salt and water retention in CHF has been established in double-blind comparative studies against furosemide. Torasemide has been shown to be at least as effective as furosemide in terms of total volume of urine excreted and also has a longer duration of action. The efficacy of torasemide (in terms of improved CHF symptoms and reduced pulmonary congestion, oedema and bodyweight) has been shown in randomised controlled trials and confirmed in large postmarketing studies. In addition, data from postmarketing studies have shown that patients receiving torasemide had significantly reduced hospital admission rates compared with patients receiving furosemide. Pharmacoeconomic assessments of torasemide have focused on its effect in reducing hospitalisation. Hospitalisation costs due to CHF decreased by 86% during the 11.2-month period of torasemide treatment, compared with the 6-month period prior to treatment, in a US retrospective study assessing medical and pharmacy claims data. Overall, average monthly costs for patients decreased by 56.6% after 5.1 months (from $US1,897.28 to $US823.70 per patient per month; PPPM), and by 76% after 11.2 months (from $US1,944.76 to $US470.76 PPPM) of torasemide treatment. In the furosemide group, average monthly costs for patients increased moderately from $US227.28 to $US261.18 PPPM after 12 months. Direct comparison of the torasemide and furosemide study groups was not possible because the group receiving torasemide had much higher healthcare resource use at baseline. Compared with furosemide, torasemide was associated with reduced rates of hospital admissions for CHF and/or cardiovascular causes in 3 studies, a retrospective analysis conducted in Germany, a prospective US study of patients enrolled from hospital admissions and a decision-analysis model. As a result, the direct costs of treatment for CHF or cardiovascular diseases for patients treated with torasemide were less than those with furosemide. However, in the US study, there was no statistically significant difference in hospital admissions for all causes and/or in overall direct medical costs, although the study was not powered to show this. In another US study of managed care patients with New York Heart Association (NYHA) class II or III CHF, no difference in clinical or economic outcomes was observed between patients taking torasemide or furosemide; despite the higher acquisition costs for torasemide, total costs were similar for both groups. Torasemide was found to be more cost effective than furosemide in terms of cost per patient with improved functional (NYHA) class of CHF severity in a retrospective German analysis, although this measure is not ideal. This study also evaluated indirect costs (for loss of productivity of employed patients) and resultssuggest torasemide has a favourable effect in reducing days off work compared with furosemide, although the population of employed patients in the study was very small. Torasemide has been shown to improve some measures of quality of life in 2 studies. It was associated with higher quality-of-life scores than furosemide in a 6-month study, but the differences were only significant at month 4. In another study, torasemide significantly improved fatigue, but full study details are yet to be published. CONCLUSIONS: Despite the higher acquisition cost of torasemide over furosemide, pharmacoeconomic analyses have shown that torasemide is likely to reduce overall treatment costs of CHF by reducing hospital admissions and readmissions. Torasemide has generally shown clinical and economic advantages over furosemide, although more long term data are needed to confirm these results and to further investigate effects on quality of life. There are limitations to the currently available pharmacoeconomic data, but present data support the use of torasemide as a first-line option for diuretic therapy in patients with CHF presenting with oedema and especially in those patients not achieving relief of symptoms with furosemide.     

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)     

Vasodilatory action of loop diuretics: a plethysmography study of endothelial function in forearm arteries and dorsal hand veins in hypertensive patients and controls

INTRODUCTION: Intravenous administration of loop diuretics induces venodilation before the diuretic response. We investigated whether furosemide and torasemide exert a dilatory effect on arteries and veins mediated by endothelial release of nitric oxide. METHODS: We performed intermittent venous occlusion plethysmography to study forearm blood flow and dorsal hand-vein distension in response to furosemide and torasemide infusion in hypertensive patients and healthy controls. RESULTS: Furosemide increased venodilation from 0.56 +/- 0.09 to 0.88 +/- 0.06 (P=0.000) in control subjects and from 0.49 +/- 0.10 to 0.75 +/- 0.12 (P=0.000) in hypertensive patients. Torasemide increased venodilation from 0.46 +/- 0.06 to 0.70 +/- 0.11 (P=0.007) in control subjects and from 0.48 +/- 0.09 to 0.67 +/- 0.12 (P = 0.03) in hypertensive patients. Co-infusion of the Nitric Oxide Synthase Inhibitor (L-NMMA)-blocked this venodilation, and the action was reversed with L-arginine. There were no significant changes in the arterial bed. CONCLUSIONS: Furosemide and torasemide induce a similar dose-response curve venodilation, but they have no effect on the arterial bed. Hypertensive patients show a smaller venous endothelium-dependent response than healthy controls. The venodilation induced by both diuretics requires release of nitric oxide.     

托拉塞米与呋塞米治疗创伤性脑水肿的临床对比观察

目的观察托拉塞米与呋塞米在治疗创伤后重型颅脑损伤后脑水肿的临床疗效及颅内压、电解质变化。方法将我科2010年9月到2011年9月收住的80例颅脑损伤引起脑水肿患者完全随机分为托拉塞米组和呋塞米组,各40例。在维生素水、电解质及酸碱平衡,清除自由基,脑保护等治疗基础上,托拉塞米组患者给予托拉塞米20mg加入0．9％氯化钠注射液10ml静脉推注,呋塞米组患者给予呋塞米20mg＋20％甘露醇125ml静脉推注。2组均1次／6h,然后根据病情变化随时调整剂量。疗程均为14d。观察用药前后颅内压的变化,同时观察尿量增加程度和临床疗效。结果托拉塞米组总有效率明显高于呋塞米组[92．5％（37／40）比62．5％（25／40）,P〈0．05]。2组治疗第1天始,尿量即开始增加,用药第1～7天,患者尿量均高于用药前,差异有统计学意义（P〈0．05）。用药第2～7天,托拉塞米组患者尿量均明显高于呋塞米组[（3489±291）ml比（3389±271）ml,（3716±431）ml比（3509±321）ml,（3869±372）ml比（3609±328）ml,（3815±429）ml比（3689±151）ml,（3792±341）ml比（3709±311）ml,（3787±411）ml比（1699±621）ml,均P〈0．05]。用药第1～7天,托拉塞米组患者颅内压均明显低于呋塞米组[（17．9±1．1）mmHg（1mmHg=0．133kPa）比（18．3±1．0）mmHg,（16．7±0．9）mmHg比（17．9±0．7）mmHg,（15．9±0．6）mmHg比（17．1±0．5）mmHg,（15．5±0．7）mmHg比（16．6±1．3）mmHg,（14．8±0．6）mmHg比（15．8±0．9）mmHg,（14．8±0．7）mmHg比（15．4±1．5）mmHg,（14．3±0．8）himHg比（15．7±0．8）mmHg,均P〈0．05]。托拉塞米组电解质紊乱发生率明显低于呋塞米组[7．5％（3／40）比20．0％（8／40）,P〈0．05]。结论托拉塞米治疗创伤性脑水肿可明显降低颅内压,增加尿量,提高疗效。     

Healthcare costs of patients with heart failure treated with torasemide or furosemide

OBJECTIVE: To compare the direct healthcare costs of patients with congestive heart failure (CHF) prescribed torasemide (torsemide) or furosemide (frusemide). DESIGN AND SETTING: As part of a prospective, randomised, nonblind study, we assessed the effects of torasemide and furosemide on readmission to hospital in 193 patients treated for CHF at a US urban public healthcare system. We also calculated total direct healthcare costs for the 2 drugs. The perspective of the analysis was that of the healthcare system. Healthcare charge and utilisation data, demographic information, and health status data were obtained from an electronic database containing data for all patients treated within the healthcare system. PATIENTS AND PARTICIPANTS: Upon admission to the hospital, patients were eligible if they had evidence of left ventricular systolic dysfunction, were at least 18 years old, and were receiving furosemide. INTERVENTION: Inpatients were randomised to either torasemide or furosemide treatment for 1 year. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with torasemide had fewer hospital admissions than those treated with furosemide [18 vs 34% for CHF (p = 0.013) and 38 vs 58% for any cardiovascular cause (p = 0.005)]. In the torasemide group, expected annual hospital costs per patient were lower for CHF admissions (by $US1054; 1998 values) and for all cardiovascular admissions (by $US1545) than in the furosemide group. Because the annual acquisition cost of torasemide was $US518 per patient higher than that of furosemide, the resulting net cost saving per patient was $US536 for CHF and $US1027 for all cardiovascular causes. Outpatient costs did not differ between treatment groups regardless of whether drug costs were considered. Total direct costs were $US2124 lower with torasemide than with furosemide (not statistically significant). CONCLUSIONS: Owing largely to reduced readmission to the hospital, the cost of inpatient care for patients with CHF is significantly lower with torasemide than with furosemide, despite the higher acquisition cost of torasemide. Treatment with torasemide resulted in a nonsignificant reduction in total direct costs (outpatient plus inpatient) compared with furosemide.     

Anti-aldosteronergic effect of torasemide.

The diuretic actions of torasemide and furosemide were studied in normotensive rats and in deoxycorticosterone acetate (DOCA)-saline-loaded hypertensive rats. Torasemide (0.3-3 mg/kg) and furosemide (3-30 mg/kg) had a dose-dependent and significant diuretic action in normotensive rats. Potassium retention was only observed in the case of torasemide. Torasemide also had a dose-dependent and significant diuretic action in DOCA-saline-loaded hypertensive rats, whereas furosemide did not. Higher doses of torasemide (10 mg/kg) and furosemide (100 mg/kg) increased both plasma renin activity and aldosterone concentration in normotensive rats in a similar manner. In vivo aldosterone receptor binding was determined to test the possible anti-aldosteronergic effect of torasemide. Torasemide inhibited the binding of aldosterone to its receptor in the cytoplasmic fraction of rat kidney in a dose-dependent manner, while furosemide produced no effect. These results suggest strongly that an anti-aldosteronergic action of torasemide contributes to producing less kaliuresis.     

Diuretic action of the novel loop diuretic torasemide in the presence of angiotensin II or endothelin-1 in anaesthetized dogs.

The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on renal haemodynamics and excretory responses in the presence of angiotensin II and endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1 was continuously infused into the renal artery throughout the experiment and a bolus of torasemide or furosemide was injected into the bracheal vein. Continuous intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1 min-1, increased renal vascular resistance (RVR) and decreased renal blood flow (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean arterial pressure (MAP). Urinary excretion of sodium (UNaV) and urine flow (UF) were significantly decreased during angiotensin II infusion. Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a decrease in RVR was accompanied by an increase in RBF. UKV was greater in the furosemide group than in the torasemide group, despite both groups having the same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin II on renal haemodynamics; however, the onset of action was extremely slow compared with the effects produced by angiotensin II. Endothelin-1 caused a significant decrease in UF, UNaV and UKV only at a later period, despite a relatively early depression of renal haemodynamics. Torasemide and furosemide also produced a sufficient diuretic action in this model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of torasemide and furosemide in rats with heart failure

It has been reported that torasemide but not furosemide, may block the renin-angiotensin-aldosterone system and therefore it might attenuate myocardial remodeling accompanied by left ventricular (LV) dysfunction. We therefore compared the therapeutic effects of torasemide, a long-acting loop diuretic, and furosemide, a short-acting one, on the progression of LV remodeling in a rat model of chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM). CHF was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, rats were treated for 28 days with torasemide, furosemide, or vehicle. We investigated the effects on metabolic and neurohumoral parameters, cardiac fibrosis and remodeling in EAM rats. Diuresis was increased dose dependently by both torasemide and furosemide, showed an equipotent natriuretic effect. The urinary potassium excretion was significantly increased with furosemide in comparison to torasemide. Myocardial functional parameters were significantly improved by torasemide. Conversely, these parameters did not change in rats receiving furosemide. Torasemide suppressed LV fibrosis, myocardial protein levels of transforming growth factor-beta1, collagen III, and aldosterone synthase and improved survival rate to the control level, but furosemide did not. Moreover, both pharmacological interventions significantly elevated plasma angiotensin II and decreased atrial natriuretic peptide in a dose-dependent manner. Our results demonstrate that compared with furosemide, torasemide treatment significantly improved survival rate, LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.     

Pharmacokinetics and pharmacodynamics of intravenous trasemide in mutant Nagase analbuminemic rats

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.     

托拉塞米治疗AECOPD患者心力衰竭的临床疗效及安全性分析

目的：探讨托拉塞米在治疗慢阻肺疾病急性发作期（AECOPD）患者心力衰竭的临床疗效及安全性分析。方法：选择武汉市汉口医院2012年1月-2017年1月收治的慢阻肺急性发作期患者74例。随机分成对照组和观察组各37例,在常规治疗及对症治疗的基础上观察组给予托拉塞米（南京海辰药业有限公司生产）10 mg静脉推注;对照组给予呋塞米（山东圣鲁制药有限公司生产）20 mg静脉推注,每日1次,连续使用5 d。分析两组治疗前后的24 h尿量、BNP测值、不良事件发生率。结果：治疗前对照组与观察组差异不明显;两组患者治疗前尿量的差异无显著性（P>0.05）,治疗前与治疗第5天后,两组比较尿量均较治疗前增加,差异有显著性（P<0.05）,但观察组与对照组比较,尿量增加对比,差异有显著性（P<0.05）;两组治疗后BNP的下降比较有显著性差异（P<0.05﹚, 治疗组总不良反应发生率为13.5%。对照组总不良反应发生率为32.4%。差异有显著性（P<0.05）。结论：短期静脉推注托拉塞米比呋塞米更有效缓解症状,改善心脏功能,更有效降低BNP,且不良反应发生率低,更安全有效。     

Diuretic and hypotensive actions of torasemide in hypertensive models of rat

The diuretic and the antihypertensive actions of torasemide were examined in renal and genetic hypertensive rats and compared to the effects of furosemide. Oral administration of torasemide (1 and 3 mg/kg) elicited a dose-dependent increase in the excretion of urine and electrolytes and elevated the urinary Na/K ratio in both renal and genetic hypertensive rats. Torasemide and furosemide had a similar maximum diuretic effect in the normotensive Wistar rat and the spontaneously hypertensive rat (SHR). However, the diuretic activity of furosemide was weaker in the renal hypertensive rat (RHR). Torasemide showed approximately 30 times greater diuretic potency than furosemide. Torasemide and furosemide demonstrated hypotensive action in hypertensive rat models, but not in the normotensive Wistar rat. Especially in the RHR, torasemide exhibited a more potent hypotensive action than furosemide. These results show that the diuretic and antihypertensive activities of torasemide are effective in various rat models of hypertension, while the diuretic activity of furosemide is weak in certain hypertensive rat models. © 1992 Wiley-Liss, Inc.     

呋塞米与托拉塞米间隔使用治疗慢性心力衰竭的临床观察

目的探讨呋塞米与托拉塞米间隔使用治疗慢性心力衰竭（CHF）的疗效。方法将符合纳入标准患者随机分成试验组和对照组。试验组先使用呋塞米片7 d,然后改为托拉塞米片7 d;对照组使用呋塞米片14 d。比较两组治疗14 d后总有效率、尿量、电解质及pro-BNP的差别。结果①试验组总有效率为89.66%,显著高于对照组（77.01%）,差异有统计学意义（χ^2=7.968,P=0.019）;②两组治疗后尿量较治疗前显著增加,差异有统计学意义（P〈0.05）,血钾和pro-BNP均较治疗前显著下降,差异有统计学意义（P〈0.05）;③治疗后试验组尿量和血钾显著高于对照组,差异有统计学意义（P〈0.05）,pro-BNP显著低于对照组,差异有统计学意义（P〈0.05）;④试验组总不良反应发生率及低钾血症发生率显著低于对照组,差异有统计学意义（P〈0.05）。结论呋塞米与托拉塞米间隔使用可提高CHF治疗的总有效率,增加尿量,减少电解质紊乱等不良反应。     

Torasemide. A review of its pharmacological properties and therapeutic potential.

Torasemide (torsemide) is a high-ceiling loop diuretic which acts on the thick ascending limb of the loop of Henle to promote rapid and marked excretion of water, sodium and chloride. Like furosemide (frusemide), its major site of action is from the luminal side of the cell. Torasemide is at least twice as potent as furosemide on a weight-for-weight basis, produces equivalent diuresis and natriuresis at lower urinary concentrations and has a longer duration of action, allowing once-daily administration without the paradoxical antidiuresis seen with furosemide. Torasemide also appears to promote excretion of potassium and calcium to a lesser extent than furosemide. In trials of up to 48 weeks' duration in patients with mild to moderate essential hypertension, torasemide, administered as a single daily dose, has been shown to achieve adequate blood pressure control reaching steady-state within 8 to 12 weeks. Those patients not responding initially have generally responded to a doubling of the dose. Comparative trials of up to 6 months show torasemide is as effective as indapamide, hydrochlorothiazide or a combination of triamterene/hydrochlorothiazide in maintaining control of blood pressure. Torasemide has also been used successfully to treat oedematous states associated with chronic congestive heart failure, renal disease and hepatic cirrhosis. In short term trials control of blood pressure, bodyweight and residual oedema has been sustained. Torasemide appears to be a useful alternative to furosemide in these patients, providing potent and long-lasting diuresis while being relatively potassium and calcium sparing. In clinical trials to date torasemide has been well tolerated with adverse effects of a mild, transient nature reported by only small numbers of patients. Changes in biochemical parameters have been common, including decreases in plasma sodium and potassium levels and increases in plasma creatinine and uric acid levels. These changes are typical of loop diuretics. No changes were clinically significant nor were clinically relevant changes noted in glucose metabolism, cholesterol or triglyceride levels or in haematological values. Thus, torasemide is an interesting new loop diuretic with potential use in the treatment of mild to moderate essential hypertension and of oedematous states in which diuretic therapy is warranted. Preliminary studies suggest it to be as efficacious as other diuretics in common use and to have some advantage over furosemide in duration of action and in effects on potassium and calcium. However, further long term trials in larger groups of patients are needed to delineate the place of torasemide in therapy fully, both as a single agent and in combination with other currently accepted drug regimens.     

托拉塞米在重症心脏联合瓣膜置换病人围手术期中的应用

目的:通过对比托拉塞米与呋塞米的利尿作用,探讨托拉塞米在重症心脏联合瓣膜置换病人围手术期中的应用价值。方法:重症心脏联合瓣膜置换病人60例,随机分为2组。托拉塞米组30例,男性6例,女性24例,年龄(54±s 12)a,围手术期中应用托拉塞米静脉注射治疗;呋塞米组30例,男性5例,女性25例,年龄(54±12)a,围手术期中应用托拉塞米静脉注射治疗。观察用手术前及手术后1,3,7,14d,24h尿中钾、钠、肌酐的含量。结果:手术后,2组24h尿钠、钾和肌酐含量均增高,与手术前比较差异非常显著(P<0.01);手术后3d起,托拉塞米组24h尿钾、钠含量低于呋塞米组,肌酐含量高于呋塞米组,差异非常显著(P<0.01)。不良反应发生率托拉塞米组10％(3/30),呋塞米组80％(24/30),差异非常显著(P<0.01)。结论:托拉塞米具有排钠又相对保钾的作用,减少了不良反应的发生,是一种比呋塞米更加适合于重症联合心脏瓣膜置换术病人的围手术期利尿药物。     

Determinants of steady-state torasemide pharmacokinetics: impact of pharmacogenetic factors, gender and angiotensin II receptor blockers

BACKGROUND: Torasemide is frequently used for the treatment of hypertension and heart failure. However, the determinants of torasemide pharmacokinetics in patients during steady-state conditions are largely unknown. We therefore explored the impact of genetic polymorphisms of cytochrome P450 (CYP) 2C9 (CYP2C9) and organic anion transporting polypeptide (OATP) 1B1 (SLCO1B1), gender, and the effects of losartan and irbesartan comedication on the interindividual variability of steady-state pharmacokinetics of torasemide. PATIENTS AND METHODS: Twenty-four patients receiving stable medication with torasemide 10 mg once daily and with an indication for additional angiotensin II receptor blocker (ARB) treatment to control hypertension or to treat heart failure were selected. Blood samples were taken before torasemide administration and 0.5, 1, 2, 4, 8, 12 and 24 hours after administration. After this first study period, patients received either irbesartan 150 mg (five female and seven male patients aged 69+/-8 years) or losartan 100 mg (two female and ten male patients aged 61+/-8 years) once daily. After 3 days of ARB medication, eight blood samples were again collected at the timepoints indicated above. The patients' long-term medications, which did not include known CYP2C9 inhibitors, were maintained at a constant dose during the study. All patients were genotyped for CYP2C9 (*1/*1 [n=15]; *1/*2 [n = 4]; *1/*3 [n=5]) as well as for SLCO1B1 (c.521TT [n=13]; c.521TC [n=11]). RESULTS: Factorial ANOVA revealed an independent impact of the CYP2C9 genotype (dose-normalized area under the plasma concentration-time curve during the 24-hour dosing interval at steady state [AUC(24,ss)/D]: *1/*1 375.5+/-151.4 microg x h/L/mg vs *1/*3 548.5+/-271.6 microg x h/L/mg, p=0.001), the SLCO1B1 genotype (AUC(24,ss)/D: TT 352.3+/-114 microg x h/L/mg vs TC 487.6+/-218.4 microg x h/L/mg, p<0.05) and gender (AUC(24,ss)/D: males 359.5+/-72.2 microg x h/L/mg vs females 547.3+/-284 microg x h/L/mg, p<0.01) on disposition of torasemide. Coadministration of irbesartan caused a 13% increase in the AUC(24,ss)/D of torasemide (p=0.002), whereas losartan had no effect. CONCLUSION: This study shows that the CYP2C9*3 and SLCO1B1 c.521TC genotype and female gender are significant and independent predictors of the pharmacokinetics of torasemide. Coadministration of irbesartan yields moderate but significant increases in the torasemide plasma concentration and elimination half-life.     

托拉塞米在肾移植病人围手术期的应用

目的:通过对比托拉塞米与呋塞米的利尿作用,探讨托拉塞米在肾移植病人围手术期中的应用价值。方法:肾移植术后病人52例,分为2组。托拉塞米组26例,男性16例,女性10例,年龄(31±s 10)a,围手术期中应用托拉塞米100 mg+氯化钠注射液500 mL,iv,qd;呋塞米组26例,男性15例,女性11例,年龄(29±9)a,围手术期中应用呋塞米400 mg·d~(-1)+氯化纳注射液500 mL,iv,qd。2组均治疗7 d为一个疗程。观察手术前和术后每日尿钾、钠及血钾、钠的含量,血压、血肌酐和24 h尿量变化情况。监测2组病人环孢素全血谷值血药浓度。结果:手术后托拉塞米组24 h尿钠、血钠含量和血肌酐与呋塞米组比较,无显著差异(P>0.05)。托拉塞米组血钾的含量和24 h尿量高于呋塞米组,差异非常显著(P<0.01)。呋塞米组24 h尿钾含量高于托拉塞米组,差异非常显著(P<0.01)。2组血压和环孢素全血谷值血药浓度比较无显著差异(P>0.05)。不良反应发生率托拉塞米组8%(2/26),呋塞米组69%(18/26),差异非常显著(P<0.01)。结论:托拉塞米具有排钠又相对保钾的作用,在增加病人尿量的同时不影响环孢素全血谷值血药浓度,减少了肾移植病人不良反应的发生,是一种比呋塞米更加适合肾移植围手术期利尿药物。