No abstract available.
Myocardial Infarction* ; Trimetazidine*

OBJECTIVES: To evaluate the efficacy of trimetazidine dihydrochloride as a treatment for chronic tinnitus. METHODS: A total of 97 chronic tinnitus patients were evaluated in this randomized, prospective, double-blind, placebo-controlled trial. After assessing for eligibility, 82 patients were randomly assigned into placebo or trimetazidine groups according to the medication. The trimetazidine group received 20×3 mg/day per oral trimetazidine dihydrochloride and the placebo group received 20×3 mg/day per oral placebo for 3 months. Tinnitus handicap inventory (THI), visual analogue scale (VAS) questionnaires and audiometric results were used to determine the effectiveness of trimetazidine treatment. RESULTS: The study group comprised 82 tinnitus subjects, 42 (51%) of whom received trimetazidine dihydrochloride and 40 (49%) who received placebo. There was no significant difference between placebo and trimetazidine groups in THI grade and VAS (both pre- and posttreatment scores) (P>0.05) and no significant improvement was observed in subjective loudness score in either group (P>0.05). Additionally there was no significant difference between groups in pre- and posttreatment pure tone hearing thresholds at all measured frequencies (P>0.05). CONCLUSION: Trimetazidine dihydrochloride therapy was ineffective for relieving chronic tinnitus.
Double-Blind Method* ; Hearing ; Humans ; Prospective Studies ; Tinnitus* ; Trimetazidine*

BACKGROUND: Trimetazidine(Vastinan(R)) is a new antianginal agent of different action mechanism specifically targeted at the metabolic cellular consequences of myocardial ischemia. The clinical efficacy of the Trimetazidine in angina pectoris is still to be defined. METHOD: To determine the antianginal effect of trimetazidine in the treatment of ischemic heart disease, 15 patients with stable angina(12 male, 3 female, mean age : 59.3 years) were studied. In 6 cases as a single agent and in 9 cases as an additive regimen to conventional antianginal medications. Trimetazidine(20mg 3 times daily) was given for 30 days or more to evaluate the clinical effect. Graded exercise tests were carried out before the trial of Trimetazidine and on the 30th day of the treatment period. RESULTS: 1) The number of episodes of anginal attacks decreased from 4.2+/-2.7 to 2.0+/-0.5 a week(p<0.05) after treatment with Trimetazidine. 2) Trimetazidine also significantly increased the duration of total exercise from 12.1+/-4.7 min to 14.5+/-3.3 min(p<0.05), and the time to 1mm ST segment depression from 7.7+/-5.9 min to 11.7+/-5.2 min(p<0.05) on treadmill exercise by modified Bruce protocol. 3) Total workload (METs) and rate pressure double product(heart rate x systolic blood pressure) slightly increased, but the differences were not significant statistically. 4) No serious clinical side effects were observed during the treatment. CONCLUSION: These results suggest that the Trimetazidine is an effective and safe as an antianginal drug in the treatment of stable angina patients as a single agent and as an additive regimen when the patients are refractory to conventional drugs.
Angina Pectoris ; Angina, Stable* ; Depression ; Exercise Test ; Female ; Humans ; Male ; Myocardial Ischemia ; Trimetazidine

OBJECTIVETo compare the pharmacokinetics and bioequivalence between domestic hydrochloric trimetazidine capsules and imported hydrochloric trimetazidine tablets in healthy male Chinese volunteers after single oral administration.

METHODSA single oral dose (test and reference formulations) was given to 24 healthy male Chinese subjects according to an open randomized crossover design. The blood samples were collected before and after administration. Plasma trimetazidine concentration was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated by WinNonlin Ver 6.2.1 software.

RESULTSThe main pharmacokinetic parameters of domestic and imported formulation of trimetazidine were similar: C(max) (70.9 ± 15.3), (66.4 ± 13.8) µg/ml; t(max) (1.70 ± 0.72), (1.85 ± 0.55) h; t(1/2z) (4.70 ± 1.75), (4.77 ± 1.96) h; AUC(0-24 h) (481 ± 176), (469 ± 171) µg×h×ml(-1); AUC(0-∞) (511 ± 189), (500 ± 188) µg×h×ml(-1). The estimated 90% CIs for the ratio of C(max) and AUC(0-24 h) were also similar: 101.9% - 112.5% and 99.4% - 104.9%. The relative bioavailability of domestic formulation was (102.2 ± 8.3)%.

CONCLUSIONThe results demonstrates that the domestic hydrochloric trimetazidine capsules and imported hydrochloric trimetazidine tablets are bioequivalent.

Adult ; Cross-Over Studies ; Humans ; Male ; Plasma ; chemistry ; metabolism ; Therapeutic Equivalency ; Trimetazidine ; blood ; pharmacokinetics

BACKGROUND AND OBJECTIVES: Tinnitus is noise from ear or head without any external sound stimulation and can cause hearing difficulties, psychogenic disturbances or many difficulties in everyday life. The etiology of tinnitus is yet to be described and the management is also very difficult. Our study was performed to evaluate the characteristics and the management of idiopathic tinnitus. MATERIALS AND METHODS: One hundred forty five patients (163 ears)with idiopathic tinnitus were entered into our department's database between Nov. 1995 and Oct. 1997. Patients were treated with drugs (dimenhydrinate, trimetazidine, diazepam, ginko biloba extract), the stellate ganglion block (SGB) or stellate ganglion block combined with drugs (combined therapy). RESULTS: It was found that (1) the average age was 53.3 years: (2) there was no laterality: (3) the buzzing sound was the most common: (4) the average symptom duration was 486 days: (5) the most common loudness was 30-49dB: (6) the most common frequency was 4-5.9 KHz: (7) the treatment with drugs was effective in 28.0%: (8) the treatment of SGB was effective in 32.8%: (9) the combined therapy was effective in 41.8%: (10) there was no statistical significance among three groups. CONCLUSION: Although there was no statistical significance, SGB was more effective than drugs whereas the combined therapy was more effective than either drugs or SGB. Therefore, SGB could be considered as another therapeutic modality in idiopathic tinnitus.
Diazepam ; Ear ; Ginkgo biloba ; Head ; Hearing ; Humans ; Noise ; Stellate Ganglion* ; Tinnitus* ; Trimetazidine

INTRODUCTION: Contrast-induced nephropathy (CIN) is a serious but preventable complication of coronary procedures. Trimetazidine (TMZ) has recently been explored for use in preventing post-procedural CIN due to its cellular anti-ischemic and antioxidant properties. The objective is to assess the efficacy of oral TMZ in the prevention of contrast induced nephropathy during elective coronary angiography and PCI among patients with renal impairment.

METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials, Pubmed/ MEDLINE, EMBASE, clinicaltrials.gov for articles published until June 2016 for randomized controlled trials examining the effects of adding oral TMZ to standard therapy in preventing CIN. Outcome measures were incidence of CIN, defined as a 0.5 mg/dl or ?25% increase in serum creatinine 48-72 hours after contrast exposure, and incidence of dialysisrequiring CIN. Validity of studies was assessed through a risk assessment tool available from Cochrane. Treatment effect was estimated by calculating the Mantel-Haenszelweighted risk ratio (RR) using a fixed-effects model available from RevMan 5.3.

RESULTS: A total of four studies comprising 714 patients (TMZ group=352, Control group=362) were included in the final analysis. Pooled results revealed the TMZ group was associated with significantly fewer incidences of CIN compared to control (RR 0.33, 95% confidence interval [CI], 0.20, 0.53; P<.00001), with a relative risk reduction of 67% and an absolute risk reduction of 11.04% (NNT=nine). No dialysis-requiring CIN was observed in the included studies.

CONCLUSION: The addition of oral TMZ to standard hydration confers a significant benefit in preventing CIN after coronary procedures among patients with mild to moderate renal impairment. We recommend the addition of TMZ to standard prevention strategies. However, a large well-designed trial should be conducted to determine its effect on other outcomes such as prevention of dialysis-requiring CIN and mortality. 

Human ; Trimetazidine ; Coronary Angiography ; Medline ; Creatinine ; Pubmed ; Risk Assessment ; Renal Insufficiency ; Kidney Function Tests

BACKGROUND AND OBJECTIVES: Studies reveal that the microvolt T wave alternans (MTWA) test has a high negative predictive value for arrhythmic mortality among patients with ischemic or non-ischemic cardiomyopathy. In this study, we investigate the effects of trimetazidine treatment on MTWA and several echocardiographic parameters in patients with stable coronary artery disease. SUBJECTS AND METHODS: One hundred patients (23 females, mean age 55.6±9.2 years) with stable ischemic heart disease were included in the study group. Twenty-five age- and sex-matched patients with stable coronary artery disease formed the control group. All patients were stable with medical treatment, and had no active complaints. Trimetazidine, 60 mg/day, was added to their current treatment for a minimum three months in the study group and the control group received no additional treatment. Pre- and post-treatment MTWA values were measured by 24 hour Holter testing. Left ventricular systolic and diastolic functions were assessed by echocardiography. RESULTS: After trimetazidine treatment, several echocardiographic parameters related with diastolic dysfunction significantly improved. MTWA has been found to be significantly improved after trimethazidine treatment (63±8 µV vs. 53±7 µV, p<0.001). Abnormal MTWA was present in 29 and 11 patients pre- and post-treatment, respectively (p< 0.001). CONCLUSION: Trimetazidine improves MTWA, a non-invasive determinant of electrical instability. Moreover, several echocardiographic parameters related with left ventricular functions also improved. Thus, we can conclude that trimetazidine may be an effective agent to prevent arrhythmic complications and improve myocardial functions in patients with stable coronary artery disease.
Cardiomyopathies ; Coronary Artery Disease* ; Coronary Vessels* ; Echocardiography ; Electrocardiography ; Female ; Humans ; Mortality ; Myocardial Ischemia ; Trimetazidine* ; Ventricular Function, Left

OBJECTIVES: Trimetazidine (TMZ) is known to reduce the generation of oxygen-derived free radicals. The objective of the present study was to evaluate the effects of TMZ on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). METHODS: Five-day, postfertilization zebrafish larvae were exposed to 125 microM neomycin and one of the following TMZ concentrations for 1 hour: 10 microM, 100 microM, 500 microM, 1,000 microM, 1,500 microM, or 2,000 microM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of hair cells in the control group that were not exposed to neomycin. Ultrastructural changes were evaluated using scanning electron microscopy. RESULTS: TMZ protected against neomycin-induced hair cell loss in the neuromasts (TMZ 1,000 microM, 11.2+/-0.4 cells; 125 microM neomycin only, 4.2+/-0.5 cells; n=10; P<0.05) and decreased the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. In the ultrastructural analysis, structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 microM neomycin and 1,000 microM TMZ. CONCLUSION: TMZ attenuated neomycin-induced hair cell loss in zebrafish. The results of this study suggest that neomycin induces apoptosis, and that apoptotic cell death can be prevented by treatment with tremetazidine.
Apoptosis ; Cell Death ; Cell Survival ; DNA Nucleotidylexotransferase ; Free Radicals ; Hair* ; Larva ; Microscopy, Confocal ; Microscopy, Fluorescence ; Mitochondria ; Neomycin ; Trimetazidine* ; Zebrafish*

Apolipoprotein (apo) E deficient mouse can produce reproducible fixed stenotic primary atherosclerotic lesion, which reveals failure to remodel of vascular lumen, in the ascending aorta, external carotid, common carotid, iliac, femoral and popliteal arteries. To evaluate the effect of drugs in regarding to both prevention of primary atherosclerotic lesion and vascular remodeling, a systematic analysis of distribution of atherosclerotic lesions was undertaken in chow-fed, 9-momth-old apo E deficient mice, which was administrated drugs including asprin, methotrexate, probucol, sulodexide, diltiazem, cilazapril, trimetazidine, molsidomine, pentoxiphylline and Ginexin (R) for 7 month from 3 month-old. On gross and microscopic examination, formation of primary atheroscleotic lesions could be delated and/or prevented patially by effets of these drugs. On morphometric examination, failure to remodel forming vascular stenosis could not be seen, though relatively mild atherosclerotic lesion occured at vascular tree. These data suggest that the stenotic process in advanced atherosclerotic vessels can be delayed and/or prevented by several drugs including methotrexate, probucol, sulodexide, diltiazem, cilazapril, trimetazidine, molsidomine, pentoxiphylline and Ginexin (R) in vivo state.
Animals ; Aorta ; Apolipoproteins ; Apolipoproteins E* ; Atherosclerosis ; Cilazapril ; Constriction, Pathologic ; Diltiazem ; Humans ; Infant ; Methotrexate ; Mice ; Mice, Knockout* ; Molsidomine ; Popliteal Artery ; Primary Prevention ; Probucol ; Trimetazidine

BACKGROUND AND OBJECTIVES: There is increasing evidence to suggest that trimetazidine (TMZ) has the ability to improve ischemic heart failure by way of optimizing the heart's energy metabolism. The aim of this study was to examine the changes of the myocardial enhancement pattern by using two-phase, contrast enhanced, ECG-gated, multi-detector computed tomography (MDCT) after the administration of TMZ in a porcine myocardial infarction model. SUBJECTS AND METHODS: The porcine myocardial infarction model was created by balloon occlusion of the left anterior descending coronary artery. We randomized the swine into two groups: group I (n=7: aspirin only) and group II (n=7: aspirin plus 1 mg/kg TMZ for 4 weeks). Echocardiography and MDCT were performed and the ejection fraction (EF, %), end-systolic volume (ESV, mL) and end-diastolic volume (EDV, mL) were measured at 28 days after induction of myocardial infarction. Three enhancement patterns, including the early arterial phase defect (ED), the 4-min late enhancement (LE) and the residual defect (RD), were also investigated and those were described as class I [ED (-), RD (-), LE (+/-)], class II [ED (+), RD (-), LE (+)], and class III [ED (+), RD (+), LE (+)]. We performed histopathologic examination after sacrificing the animals. RESULTS: The baseline and follow-up echocardiography at 4 weeks after the induction of MI demonstrated no significant differences between the two groups. The LV indices by MDCT were also similar between the two groups (group I: EF, ESV and EDV=46.0+/-12.5%, 35.9+/-23.0 mL and 69.0+/-40.2 mL, respectively, group II: EF, ESV and EDV=49.8+/-13.2%, 43.8+/-23.1 mL and 82.8+/-24.6 mL, respectively, p=NS). The percent wall thickness was similar (69.1+/-19.6% vs. 64.9+/-10.5%, respectively, p=NS), but the enhancement pattern was different between the two groups (group I: class I, II and III=0 (0%), 0 (0%): and 7 (100%) respectively, group II: class I, II and III=0 (0%), 2 (28.6%) and 5 (71.4%), respectively, p<0.001). The volume of tissue that lacked triphenyl tetrazolium chloride was similar between two groups (8.4+/-1.9% vs. 7.3+/-2.6%, respectively, p=NS). CONCLUSION: TMZ administration produced different enhancement patterns on MDCT. This result suggests that TMZ administration can reduce the residual defect in a porcine myocardial infarction model. Although further experiments are needed for determining the effect of TMZ on reducing the irreversible area of infarcted myocardium, this is the first report that proved the beneficial effect of TMZ by performing MDCT.
Animals ; Aspirin ; Balloon Occlusion ; Coronary Vessels ; Echocardiography ; Energy Metabolism ; Follow-Up Studies ; Heart Failure ; Infarction ; Myocardial Infarction* ; Myocardium ; Swine ; Tomography, X-Ray Computed ; Trimetazidine*