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AIM: To explore the efficacy of torasemide combined with levocarnitine in the treatment of chronic heart failure (CHF). METHODS: From July 2018 to July 2020, 75 patients with CHF were recruited and randomly assigned into the control group (37 cases) and the study group (38 cases) according to the random number table method. The control and study groups were treated with levocarnitine and the combination of levocarnitine and torasemide, respectively. The clinical efficacy of the two groups was evaluated. The ventricular remodeling indexes and 6-minute walk test (6MWT) distance were compared between the two groups before and after treatment. The serum levels of serum galectin-3 (Gal-3), interleukin-33 (IL-33), hypersensitive C-reactive protein (hs-CRP), and the plasma concentrations of N terminal pro B type natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) were determined. RESULTS: (1) After treatment, the total clinical effective rate of the study group (92.11%) was higher than that of the control group (72.97%) (P<0.05). (2) The diastolic interventricular septal thickness (IVST) and diastolic left ventricular posterior wall thickness (LVPWT) were decreased following the treatment in both groups (P<0.05), whereas the treatment led to the increases of the left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF) in both groups (P<0.05). Compared with those in the control group, IVST and LVPWT in the study group were lower (P<0.05), and LVMI and LVEF were higher (P<0.05). (3) The levels of serum Gal-3, IL-33 and hs-CRP in the two groups were decreased after treatment (P<0.05); compared with those in the control group, the levels of serum Gal-3, IL-33 and hs-CRP were reduced to a greater extent in the study group (P<0.05). (4) Compared with that before treatment, 6MWT distance in both groups increased after treatment (P<0.05); the improvement in the study group was more significant relative to those in the control group (P<0.05). (5) Compared with before treatment, the expression levels of plasma NT-proBNP and BNP in the two groups were decreased after treatment (P<0.05); the reduction of plasma NT-proBNP and BNP levels in the study group was greater than the control group (P<0.05). CONCLUSION: Torasemide combined with levocarnitine is more effective than levocarnitine monotherapy in the treatment of CHF and can significantly improve ventricular remodeling index and motor function, reduce serum inflammation, and enhance cardiac function with definite curative effect.
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Objective: To observe therapeutic effect of torasemide combined small dose dopamine on patients with refractory heart failure (RHF). Methods: A total of 146 RHF patients, who were treated in our hospital from Jan 2015 to Sep 2016, were selected. According to random number table, they were randomly and equally divided into torasemide group and combined treatment group (received torasemide combined small dose dopamine), both groups were treated for 7d. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDd), 6min walking distance (6MWD), levels of interleukin 6 (IL-6) and tumor necrosis factorα (TNF-α) before and after treatment, and total effective rate were measured and compared between two groups. Results: Compared with before treatment, after treatment, there were significant rise in LVEF and 6 MWD, and significant reductions in LVEDd, levels of IL-6 and TNF-αin two groups, P=0. 001 all; compared with torasemide group after 7d treatment, there were significant rise in LVEF [(30. 69±4. 52) ％ vs. (36. 29±4. 86) ％]and 6MWD [(271. 21±48. 32) m vs. (322. 45±56. 34) m], and significant reductions in LVEDd [(54. 17±7. 64) mm vs. (46. 52±6. 52) mm], levels of IL-6 [(34. 65±6. 13) μg/ml vs. (26. 18±4. 53) μg/ml]and TNF-α [(50. 27±8. 74) μg/ml vs. (37. 48± 7. 04) μg/ml]in combined treatment group, P=0. 001 all. Total effective rate of combined treatment group was significantly higher than that of torasemide group (90. 4％ vs. 71. 2％, P=0. 03). Conclusion: Torasemide combined small dose dopamine can significantly reduce levels of IL-6 and TNF-α, improve cardiac function and therapeutic effect in RHF patients, which is worth extending.
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Objective To investigate the pharmacokinetics and pharmacokinetics of torsemide in children with acute heart failure.Methods Ninety cases of children with acute heart failure patients were randomly divided into three groups which were given different intravenous therapy doses of torsemide. Our goal is to provide the basis for clinical rational therapy by analyzing parameter of the pharmacokinetics and pharmacokinetics of torsemide which is acquired by detecting plasma concentration of torsemide with liquid chromatography and tandem mass spectrometry after a one-time medication. Result Average pharmacokinetic parameters of the three groups in addition to the peak concentration (Cmax) and medication in the area under the curve (AUC0-16) are different (P＜0.01), the rest of the pharmacokinetic parameters had no significant difference (P＞0.05) . The 24 hours urine volume of the experimental groupⅡand the experimental groupⅢwere obviously higher than that of the experimental groupⅠ, so the difference was statistically significant (P＜0.01).The 24 hours urine volumes between the experimental group Ⅱ and the experimental group Ⅲ were no significant difference (P＞ 0.05).There was no significant change in blood pressure, weight, abdominal girth, blood potassium, blood sodium and blood chlorine in the three dose groups compared with those before the treatment. There was no significant difference between the three groups (P＞0.05) . Conclusion The children with acute heart failure were well tolerated with torsemide. The recommended dose of torsemide is 1.0 mg/(kg.d) in the treatment of acute heart failure in children, based on pharmacokinetic and pharmacodynamic characteristics.
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Objective To compare the diuretic efficacy of torasemide as a 2-hour continuous infusion and as a bolus injection of equal dose in patients with nephrotic syndrome,and to investigate a preferable administration mode of torasemide for these patients.Methods Twenty-three hospitalized patients were randomized to receive torasemide 20 mg or 40 mg per day by either 2-hour intravenous infusion or bolus injection,and interchanged after 48 hours of washout.Results Patients received torasemide by 2-hour intravenous infusion exhibited significantly higher daily urinary volume,chloride excretion,sodium excretion and fractional excretion of sodium (FENa) within 24 hours than those by bolus injection (P ＜ 0.05).Significantly lower bound-state torasemide excretion,higher ratio of urinary volume to torasemide excretion and a markedly larger area under the curve in the plasma concentrationtime profiles were also observed in the infusion group (P ＜ 0.05).Conclusion 2-hour continuous infusion delivers a better diuretic effect compared with a bolus injection of equal dose of torasemide in patients with nephrotic syndrome.
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Objective To establish a method for determining the dissolution oftorasemide sustained-release tablet in vitro and study the methodology of the determination.The consistency of the in vitro release behavior between self-prepared torasemide sustained-release tablet and original preparation were evaluated by constructed method.Methods HPLC method was applied to detect the cumulative release percentage of self-prepared torasemide sustained-release tablet and original preparation in five kinds of release media (water,0.1 mol/L hydrochloric acid solution,pH 4.5 acetate buffer,pH 6.8 phosphate buffer,and 0.1 mol/L hydrochloric acid solution turn to pH 6.8 phosphate buffer).Similarity factor (f2) was used to evaluate the similarity of release curves.Results There was a good linear relationship between the quality concentration of torasemide and peak area in the range of 1.0-12.0 μg/mL (r =0.9995).Results of precision and stability tests were good,and the RSDs for probational liquid were all lower than 2.0％.The average recovery of accuracy test was 100.04％,and RSD was 0.54％ (n =12).The homogeneity of within group of self-prepared preparation met the technical requirement,RSDs of each sampling points in six Dissolution Vessels were lower than 10.0％.The f2 factors of self-prepared torasemide sustained-release tablet and original preparation were 72,60,77,66,and 60 in five kinds of release media.Conclusion The method in the paper is suitable for the release test of torasemide,meanwhile,the self-prepared tablet shows consistent in vitro release behavior with that of the original preparation.
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OBJECTIVE: To evaluate the bioequivalence of tested and reference torasemide tablets in healthy male volunteers. METHODS: A single oral dose of the two formulations was given to 24 healthy male volunteers according to a randomized crossover design. Plasma drug concentrations were determined by HPLC-MS. RESULTS: The pharmacokinetic parameters of torasemide of the two preparations were as follows: ρmax (1 408.29±337.27) and (1 487.86±360.24) ng·mL-1, tmax (0.90±0.42) and (1.03±0.50) h, t1/2(4.43±0.57) and (4.43±0.60) h, MRT (3.90±0.60) and (4.01±0.72) h, AUC0-24 h(3 886.86±865.99) and (3 906.06±761.72) ng·h·mL-1, AUC0-∞ (3 936.57±903.93) and (3 956.96±789.98) ng·h·mL-1, respectively. The relative bioavailability of tested torasemide tablets were (99.8±11.7)% and (99.7±12.0)% when calculated by AUC0-24 h and AUC0-∞, respectively. CONCLUSION: The two formulations of torasemide are bioequivalent in healthy Chinese volunteers.
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Objective To study the effects of photodynamic therapy (PDT) combined with torasemide on rat glioma by detecting the protein expression of matrix metalloproteinase 2 (MMP2),matrix metalloproteinase 9 (MMP9),sodium-potassium-chloride co-transporter 1 (NKCC1) and vascular endothelial growth factor (VEGF).Methods Male Wistar rats with glioma were randomly divided into four groups,includes control group (sham group,n=15),photodynamic therapy group (PDT group,n=15),torasemide group (T group,n=15) and PDT+T group (n=15).The rats were normally fed in the sham group,were received PDT (80 J/cm2) for 10 min in the PDT group,were received intraperitoneal torasemide 5 mg/kg for 3 days in the T group,and received PDT and torasemide treatment in the PDT+T group.After 2 weeks,5 rats were sacrificed from each group.Peritumoral edema tissues were harvested for the detection of wet-dry-weight ratio (W/D),and the protein expression of MMP2,MMP9,NKCC 1 and VEGF by Western Blot,immunohistochemistry and qRT-PCR.The remaining rats were used for survival time assessment.Results Compared with the sham group,the PDT group showed an increase in W/D (5.17±0.42 vs 4.83±0.38),the expression of NKCC1 (0.54±0.21 vs 0.35±0.12) and VEGF (0.68±0.20 vs 0.42±0.15),and survival time ((32.2±2.9) d vs (25.3±2.6) d) (all P＜0.05),and showed an decrease in the expression of MMP2 (2.76±0.42 vs 1.88±0.17) and MMP9 (2.55±0.38 vs 1.46±0.21) (all P＜0.05).Compared with the PDT group,the T group showed decrease in W/D (3.68±1.04),the expression of NKCC1 (0.22±0.10) and VEGF (0.33±0.14),and survival time ((28.7±2.2) d) (all P＜0.05),and showed increase in the expression of MMP2 (2.71 ±0.35) and MMP9 (2.42±0.36) (all P＜0.05).Compared with the PDT group,the PDT+T group showed decrease in W/D (4.52±0.46),and the expression of NKCC1 (0.30±0.16),VEGF (0.44±0.21),MMP2 (1.84±0.23) and MMP9 (1.53±0.24) (all P＜0.05),and showed increase in survival time ((44.5±2.8) d)(P＜0.05).Conclusion PDT combined with torasemide can reduce PDT induced edema,reduce tumor invasiveness,and prolonged the average survival time of rats.
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OBJECTIVE:To observe clinical efficacy and safety of torasemide in the treatment of chronic heart failure(CHF). METHODS:94 patients with CHF were selected and randomly divided into control group and observation group,with 47 cases in each group. Control group were treated with routine treatment,such as bed rest,oxygen inhalation,control of total body fluid in-take,routine anti-heart failure therapy and use of diuretic in 24 h. Based on the above treatment,observation group were treated with Torasemide injection with initial dose of 5-10 mg,qd,gradually increasing to 20 mg/d,maximal does of 40 mg/d. Both group re-ceived 7 days of continuous treatment. Clinical efficacies were observed in 2 groups as well as serum potassium and sodium,Scr,24 h urine volume and the rate ofⅠ-Ⅱgrade cardiac function before and after treatment. The occurrence of ADR was compared between 2 groups. RESULTS:The total effective rate of observation group was 61.70%,which was significantly higher than that of control group (46.81%),with statistical significance (P0.05). There was no statistical significance in 24 h urine volume and the rate ofⅠ-Ⅱgrade cardiac function between 2 groups before and after treatment(P>0.05);after treatment,24 h urine volume and the rate ofⅠ-Ⅱgrade cardiac function of 2 groups were increased significantly,the observation group was higher than the control group, with statistical significance (P0.05). CONCLUSIONS:Torasemide is effective for CHF,and can promote diuresis and the recovery of cardiac function with good safety.
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A sensitive and selective method using high-performance liquid chromatography coupled with elec-trospray ionization tandem mass spectrometry (HPLC–ESI–MS) to determine the concentration of tor-asemide in human plasma samples was developed and validated. Tolbutamide was chosen as the internal standard (IS). The chromatography was performed on a Gl Sciences Inertsil ODS-3 column (100 mm ? 2.1 mm i.d., 5.0 mm) within 5 min, using methanol with 10 mM ammonium formate (60:40, v/v) as mobile phase at a flow rate of 0.2 mL/min. The targeted compound was detected in negative io-nization at m/z 347.00 for torasemide and 269.00 for IS. The linearity range of this method was found to be within the concentration range of 1–2500 ng/mL (r?0.9984) for torasemide in human plasma. The accuracy of this measurement was between 94.05%and 103.86%. The extracted recovery efficiency was from 84.20% to 86.47% at three concentration levels. This method was also successfully applied in pharmacokinetics and bioequivalence studies in Chinese volunteers.
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Objective To investigate the stability of torasemide injection and predict its expiration date in room temperatue .Methods The contents of torasemide were determined by HPLC .The expiration date was predicted by classical constant-temperature experiment .Results The contents of torasemide degradation with time according to a first order reaction at room temperature (25 ℃) .The disintegration rate constant K was K25 ℃ =5 .186 9 × 10-6 h-1 and the expiration date of to-rasemide injection was t0 .9 =2 .32 years .Conclusion The torasemide injection expiration date was tentatively scheduled for two years .
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Objective To observe the short-term effect of alprostadil combined with torasemide in the treatment of intractable heart failure.Methods Thirty cases of patients with intractable heart failure and ineffective in routine therapy were given alprostadil and torasemide treatment,with alprostadil 20 mg in 5％ glucose or 0.9％ sodium chloride solution 100 ml intravenous infusion once a day and torasemide 20-40 mg intravenous twice a day 3 days later torasemide dosage was adjusted according to the disease,and the remaining conventional anti-heart failure therapy unchanged.Course was one week.The blood pressure,body weight,urine output,creatinine,electrolytes,N-terminal pro-brain natriuretic peptide (NT-proBNP)and left ventricular ejection fraction (LVEF) before and after treatment was observed.Results After treatment,clinical symptoms of dyspnea,edema,pulmonary rales,such as wet and dry significantly improved in all patients.During the course of the treatment,3 patients appeared mild hypokalemia,and potassium was promptly corrected.Body weight after treatment reduced compared with that before treatment [(63.8 ± 7.6) kg vs.(82.6 ± 10.7) kg],urine output increased after treatment compared with that before treatment [(2 328.3 ±367.8) ml/d vs.(568.7 ± 104.6) ml/d],and the differences were statistically significant (P ＜ 0.01).Systolic blood pressure,diastohc blood pressure difference was not statistically significant after treatment,compared with that before treatment (P ＞ 0.05).LVEF after treatment increased compared with that before treatment [(44.5 ± 8.3)％ vs.(31.9 ± 10.2)％],serum creatinine levels reduced [(97.8 ± 18.6) μmol/L vs.(143.8 ±21.7) μmol/L],and the difference was statistically significant (P＜ 0.05) ; NT-proBNP after treatment reduced compared with that before treatment [(567.4 ± 212.3) ng/L vs.(2 726.5 ± 525.3) ng/L],and the difference was statistically significant(P ＜ 0.01).Conclusion Alprostadil combined with torasemide treatment can quickly and effectively improve symptoms and help improve heart and kidney function in intractable heart failure,and has no significant adverse reactions.
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Objective To compare the effect of torasemide or furosemide combined with mannitol in the treatment of acute cerebral hemorrhage patients with cerebral edema.Methods One hundred and sixty patients with cerebral hemorrhage were selected,and divided into torasemide group and furosemide group according to different treatment methods,40 cases in each.The torasemide group was treated with torasemide combined with 20％ mannitol,the furosemide group was treated with furosemide combined with 20％ mannitol.The curative effect,mannitol dosage,edema volume,24 h urine and adverse reactions in two groups were compared.Results The total effective in torasemide group was higher than that in furosemide group [97.5％ (78/80) vs.77.5％ (62/80)],mannitol dosage was less than that in furesemide group [(347.5 ±32.5) ml vs.(438.2 ±30.7) ml],the incidence of adverse reactions was lower than that in furosemide group [7.5％(6/80) vs.27.5％(22/80)],which reached statistical significance (P＜ 0.01 or ＜ 0.05).The edema volume in the 7th,14th day in torasemide group was less than those in furosemide group [(21.1 ±3.4) ml vs.(23.3 ±4.8) ml,(17.6 ±4.5) ml vs.(22.4 ±5.6) ml],the 24 h urine in the 3re,7th,14th day were more than those in furosemide group [(3 684 ±528) ml vs.(3 429 ±592) ml,(3 854 ± 746) ml vs.(3 185 ±490) ml,(3 742 ±t658) ml vs.(2 251 ± 324) ml],which reached statistical significance (P ＜ 0.05).Conclusions Torasemide in treatment of acute cerebral hemorrhage patients has better efficacy and safety.It is better than furosemide.
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0.05) between the two groups.The 24 h volume of urine was significantly increased in both groups.The incidence rates of adverse drug reactions(ADR) of torasemide injection and furosemide injection were 3.88% and 2.88% respectively.CONCLUSION: Torasemide injection is an effective and safe drug for the treatment of congestive heart failure with edema.