Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Women with primary hypercholesterolaemia are often considered for lipid-lowering drug therapy at a later age than men. With regard to the prevention of cardiovascular morbidity, women can expect to receive the same benefits from lipid-lowering treatment as men. Thus, it is of interest to evaluate the efficacy, safety and tolerability of the new lipid-lowering agent fluvastatin in women. A retrospective analysis was made on the basis of data from controlled clinical trials in which 1815 patients were treated with fluvastatin at a daily dose of > or = 20 mg, and 783 patients received placebo. 782 of the fluvastatin-treated patients (43.1%) and 315 patients on placebo (40.2%) were women. Within these groups, 577 patients (73.8%) treated with fluvastatin and 183 patients receiving placebo (78.4%) were at least 50 years of age. The effect of fluvastatin 40 mg/day on low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol was more favourable in women than in men. In women, the change from baseline was -26.7% for LDL cholesterol and 5.3% for HDL cholesterol. In men, the equivalent changes from baseline were -23.8% and 4.0%, respectively. All changes from baseline were highly significant (p < 0.001). Fluvastatin lowered triglycerides to a similar extent in women and men (7.1% vs 6.9%, respectively). More women than men experienced a confirmed increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) when receiving fluvastatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy and safety of fluvastatin in women with primary hypercholesterolaemia. 751 36

Statins are regarded as a well-tolerated class of drugs, particularly when compared with some of the older lipid-modifying agents, which have poor rates of compliance. Despite some early concern, the incidence of lens opacities observed in clinical studies involving statin use is no different from that in a normal ageing population. Similarly, the occurrence of insomnia with lipophilic agents appears to have been overemphasised and is not a clinically significant problem, irrespective of the statin under study. Fluvastatin is the newest representative of this class of agents; it has already been evaluated in thousands of patients who have hyperlipidaemia with and without additional risk factors. In controlled clinical studies, the incidence of the majority of adverse events observed with fluvastatin therapy is no higher than that seen with placebo, with the exception of gastrointestinal disturbances (known to be common to all stains). Nonetheless, the incidence of these effects seen with fluvastatin treatment is noted to be lower than that associated with cholestyramine or fibrate use. Elevations in levels of liver transaminases (aspartate aminotransferase and alanine aminotransferase) have been reported with fluvastatin therapy but have led to discontinuation of treatment with the same frequency as with placebo. Elevations in creatine kinase levels as a cause of discontinuing fluvastatin are not more frequent than with placebo. Drug-related myopathy and rhabdomyolysis have not been reported with fluvastatin therapy, and myalgia does not occur more frequently than with placebo. In terms of drug interactions, fluvastatin does not interfere with the efficacy of antihypertensive agents. In controlled clinical trials, the overall reported discontinuation rate due to adverse events noted with fluvastatin therapy is not significantly distinguishable from the rate associated with placebo.
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PMID:Safety profile of fluvastatin. 1948 70

Fluvastatin, a new synthetic inhibitor of HMGCoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, has been studied in several models to examine its effects when used in combination with other lipid-modifying agents such as derivatives of fibric acid (bezafibrate), resins (cholestyramine), and niacin. The combination of fluvastatin with bezafibrate has been studied in a double-blind trial involving patients with well-documented familial hypercholesterolaemia. Fluvastatin 40 mg/day, combined with either bezafibrate 400 mg/day or cholestyramine 8 g/day, resulted in reductions in levels of low-density lipoprotein cholesterol (LDL-C), these being indistinguishable between the groups; however, significantly greater increases in levels of high-density lipoprotein cholesterol (21.3%) and reductions in levels of triglycerides (25.1%) were seen with the fluvastatin-bezafibrate combination. No notable increases were seen in levels of serum creatine kinase, aspartate aminotransferase, or alanine aminotransferase, and no cases of myopathy were observed. In a study model that examined low-dose combinations of fluvastatin with cholestyramine, reductions in levels of LDL-C of 15.8% and 19.3% were seen with fluvastatin 10 mg and 20 mg, respectively. After an 8-week interval in which a daily dosage of cholestyramine 8 g was added, from baseline, reductions of 26.3% in the 10 mg fluvastatin-cholestyramine group and 31.2% in the 20 mg fluvastatin-cholestyramine group were observed, whereas the placebo-cholestyramine group displayed a reduction of 14.9%. Doubling the resin dosage to 16 g/day for the final 8 weeks of the study provided little additional benefit. Myotoxicity has been observed when lovastatin is coadministered with niacin, and so the combination of niacin with fluvastatin has also been studied to examine the possibility of this effect occurring. Patients were randomised to either fluvastatin 20 mg or placebo for 6 weeks, after which time open-label niacin was administered to all patients and titrated to a final dosage of 3 g/day. After 6 weeks, fluvastatin produced a 20.8% reduction in LDL-C levels from baseline. When combined with niacin, a 43.7% reduction was noted at the week 15 endpoint, against the 26.5% reduction seen with niacin monotherapy. The combination was well tolerated, with no reports of myopathy or of significant elevations in creatine kinase or liver transaminase levels. Combinations of fluvastatin with a variety of other agents have been shown to have significant effects on lipid profiles, with no evidence to date of clinically remarkable safety findings. Thus, the use of combination therapies may result in optimal management of patients with moderately severe hypercholesterolaemia and mixed dyslipidaemic profiles.
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PMID:Fluvastatin in combination with other lipid-lowering agents. 1949 70

The objective of this open trial was to investigate the efficacy and safety of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin in hypercholesterolemic patients already receiving probucol. All of the participants had hypercholesterolemia. i.e. serum total cholesterol > or = 220 mg/dl, despite administration of probucol, 500 mg/day, for more than 4 weeks. After this, fluvastatin, 30 mg/day, was added to probucol treatment for 12 weeks. Twenty-seven patients were recruited into this study; all were evaluated for safety, and 22 were evaluated for efficacy. The addition of fluvastatin to the probucol regimen produced a significant further reduction in serum total and low-density lipoprotein cholesterol concentrations (of 18 and 20%, respectively; p < 0.001); these effects were fully established within 4 weeks of treatment and were maintained throughout the treatment. Fluvastatin did not affect the serum high-density lipoprotein cholesterol concentration. Fluvastatin treatment decreased serum triglyceride concentrations slightly in all patients (not significant); in patients with hypertriglyceridemia, triglyceride levels were decreased significantly by 34% (p < 0.01; serum triglycerides > or = 150 mg/dl). In addition, fluvastatin significantly decreased serum apolipoprotein B, C-II, C-III and E levels, whereas serum apolipoprotein A-I and A-II levels were unaffected. One patient complained of slight abdominal discomfort during fluvastatin administration, but relationship to fluvastatin remains unclear. One patient had slight elevation of the serum alanine aminotransferase level, and another patient had an elevated gamma-glutamyl transferase level. The addition of fluvastatin to probucol treatment can be considered to be an effective and well tolerated treatment in hypercholesterolemic patients.
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PMID:Efficacy and safety of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin in hyperlipidemic patients treated with probucol. 909 17

Hyperlipidaemia of 18 male and 20 female patients following successful renal transplantation was treated with daily 20 mg fluvastatin (Lescol) for 12 weeks. The patients were several months after transplantation, and their total cholesterol levels exceeded 6.5 mmol/l following an 8-week diet. The effect of fluvastatin on the levels of total cholesterol, HDL, LDL, triglyceride, Apo A1 and Apo B, as well as of lipoprotein(a) was examined. Furthermore, changes of the renal function (GFR-urea, creatinine, uric acid) and hepatic function (bilirubin, GOT, GPT, CPK, ALP) were followed up, together with the body weight and blood pressure. The results of the examinations are summarized as follows: Fluvastatin may be administered effectively and without side effects in a daily dose of 20 mg in appropriately selected renal transplant patients. The average total cholesterol values, which were 7.91 mmol/l in men and 7.78 mmol/l in women following the diet, were reduced by 22-25% (p < 0.001) after 6 and 12 weeks, respectively, of fluvastatin treatment. The levels of LDL also decreased significantly (p < 0.001): in response to a 20 mg evening dosage, reduction of more than 25% was observed in 78% of men and 65% of women. Reductions of the Apo B levels were more pronounced in the females (18.3% men vs. 21.2% women). The ratio C/HDL-C decreased both in men (from 5.49 to 4.19) and in women (from 4.83 to 4.02). The ratio Apo B/Apo A1 also decreased (men: from 0.86 to 0.73, women: from 0.73 to 0.66). The concentrations of HDL and Apo A1 did not increase significantly, the reductions in the levels of triglyceride and lipoprotein(a) were not considerable either. An increase in the levels of hepatic enzymes and CPK was not encountered during the administration of fluvastatin. In two patients the levels of serum bilirubin increased by 2-4 micromol/l. Three patients complained about temporary myalgias of the sacroiliac or lumbar region which, however, were not accompanied by elevated CPK levels. The monitored levels of cyclosporine, urea and creatinine did not increase significantly during the 12 weeks of treatment. Two patients had temporary gastric complaints.
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PMID:Fluvastatin (Lescol) treatment of hyperlipidaemia in patients with renal transplants. 920 45

High serum cholesterol and LDL-cholesterol level and high blood pressure are risk factors for cardiovascular disease (CVD). CVD risk factors usually occur simultaneously, fact that enhance personal and population CVD risk. Data from interventional studies suggest that reducing CAD risk factors significantly lowered risk of CAD. Fluvastatin, a statine, has been used in hypercholesterolemic populations. We report on a clinical trial (random selection) of fluvastatin vs. placebo on hipercholesterolemic patients (total cholesterol > or = 240 mg/dl and/or low-density lipoprotein cholesterol (LDL-C) > or = 160 mg/dl) on treatment of mild to moderate high blood pressure. Forty Latin-American patients were randomized to placebo or 40 mg per day for 8 weeks of fluvastatin. Fluvastatin patients had a clinical and statistical significant reduction on total cholesterol (27.7%) and LDL-C (39.1%) Vs a non-significant reduction on the placebo group (6.9% total cholesterol and 9.1% LDL-C). One patient had elevated aspartate (AST) and alanine (ALT) aminotransferases (three times the local laboratory upper normal levels) associated with a chronic alcohol consumption, reverted 6 weeks after protocol completion. There was no important secondary effects; also there was no differences on this regard between placebo and verum group. Fluvastatin proved to be safe and well tolerated for this group of patients under a wide range of high blood pressure treatment.
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PMID:[Clinical trial with sodium fluvastatin in patients with hypercholesterolemia associated with mild and moderate essential arterial hypertension]. 929 41

Preliminary data suggest that fluvastatin may be safely combined with fibrates. The Fluvastatin Alone and in Combination Treatment Study examined the effects on plasma lipids and safety of a combination of fluvastatin and bezafibrate in patients with coronary artery disease and mixed hyperlipidaemia. A total of 333 patients were randomly allocated in this multicentre double-blind trial to receive 40 mg fluvastatin alone (n=80), 400 mg bezafibrate (n=86), 20 mg fluvastatin+400 mg bezafibrate (n=85) or 40 mg fluvastatin+400 mg bezafibrate (n=82) for 24 weeks. Low-density lipoprotein (LDL)-cholesterol decreased >20% in all fluvastatin-containing regimens, with significantly greater decreases compared with bezafibrate alone (P<0.001). Bezafibrate alone and fluvastatin+bezafibrate combinations resulted in greater increases in high-density lipoprotein (HDL)-cholesterol and decreases in triglycerides compared with fluvastatin alone (P<0.001). Fluvastatin (40 mg)+bezafibrate was the most effective for all lipid parameters with a decrease from baseline at endpoint in LDL-cholesterol of 24%, a decrease in triglycerides of 38% and an increase in HDL-cholesterol of 22%. All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy, or between combination regimens. No clinically relevant liver (aspartate aminotransferase [ASAT] or alanine aminotransferase [ALAT]) greater than three times the upper limit of normal) or muscular (creatine phosphokinase (CPK) greater than four times the upper limit of normal) laboratory abnormalities were reported. This large study shows 40 mg fluvastatin in combination with 400 mg bezafibrate to be highly effective and superior to either drug given as monotherapy in mixed hyperlipidaemia, and to be safe and well tolerated.
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PMID:Efficacy and safety of a combination of fluvastatin and bezafibrate in patients with mixed hyperlipidaemia (FACT study). 1129 92

Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, and its metabolites have been reported to protect against oxidative DNA damage in vitro. Streptozotocin (STZ) has drawn attention as a potential source of oxidative stress that induces genotoxicity. In order to elucidate the antioxidative effects of fluvastatin in vivo, we investigated the effects of 7-day treatment with fluvastatin on DNA damage in STZ-treated mice, as well as the effects of the main fluvastatin metabolites (M2, M3 and M4) and other inhibitors of the same enzyme, pravastatin and simvastatin. Protective effects against DNA damage in the liver and kidney from STZ-treated mice were assessed by the single-cell gel electrophoresis assay, and by detecting 8-hydroxy-2'-deoxyguanosine. A single intraperitoneal injection of STZ (150 mg/kg) increased serum levels of glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and blood urea nitrogen (BUN), and also caused DNA damage in the liver and kidney. Fluvastatin and its metabolites prevented the STZ-induced elevation of DNA damage and inhibited the increase in serum levels of AST, ALT and BUN. Fluvastatin and its metabolites showed protective effects against DNA damage as potent as that of the reference antioxidants (ascorbic acid, trolox and probucol) though pravastatin and simvastatin still lacked protective activity. Fluvastatin protected the mice against STZ-induced DNA damage, and may reduce the risk of oxidative stress in vivo.
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PMID:Antioxidative effects of fluvastatin and its metabolites against DNA damage in streptozotocin-treated mice. 1238 3

Statins are regarded as a well-tolerated class of drugs, particularly when compared with some of the older lipid-modifying agents, which have poor rates of compliance. Despite some early concern, the incidence of lens opacities observed in clinical studies involving statin use is no different from that in a normal ageing population. Similarly, the occurrence of insomnia with lipophilic agents appears to have been overemphasised and is not a clinically significant problem, irrespective of the statin under study. Fluvastatin is the newest representative of this class of agents; it has already been evaluated in thousands of patients who have hyperlipidaemia with and without additional risk factors. In controlled clinical studies, the incidence of the majority of adverse events observed with fluvastatin therapy is no higher than that seen with placebo, with the exception of gastrointestinal disturbances (known to be common to all stains). Nonetheless, the incidence of these effects seen with fluvastatin treatment is noted to be lower than that associated with cholestyramine or fibrate use. Elevations in levels of liver transaminases (aspartate aminotransferase and alanine aminotransferase) have been reported with fluvastatin therapy but have led to discontinuation of treatment with the same frequency as with placebo. Elevations in creatine kinase levels as a cause of discontinuing fluvastatin are not more frequent than with placebo. Myopathy and rhabdomyolysis have not been reported with fluvastatin therapy, and myalgia does not occur more frequently than with placebo. In terms of drug interactions, fluvastatin does not interfere with the efficacy of antihypertensive agents. In controlled clinical trials, the overall reported discontinuation rate due to adverse events noted with fluvastatin therapy is 3.3%, which is not significantly distingushable from the rate associated with placebo (3.5%)2.
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PMID:Safety profile of fluvastatin. 872 86

Fluvastatin, a new synthetic inhibitor of HMGCoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, has been studied in several models to examine its effects when used in combination with other lipid-modifying agents such as derivatives of fibric acid (bezafibrate), resins (cholestyramine), and niacin. The combination of fluvastatin with bezafibrate has been studied in a double-blind trial involving patients with well-documented familial hypercholesterolaemia. Fluvastatin 40 mg/day, combined with either bezafibrate 400 mg/day or cholestyramine 8 g/day, resulted in reductions in levels of low-density lipoprotein cholesterol (LDL-C), these being indistinguishable between the groups; however, significantly greater increases in levels of high-density lipoprotein cholesterol (21.3%) and reductions in levels of triglycerides (25.1%) were seen with the fluvastatin-bezafibrate combination. No notable increases were seen in levels of serum creatine kinase, aspartate aminotransferase, or alanine aminotransferase, and no cases of myopathy were observed. In a study model that examined low-dose combinations of fluvastatin with cholestyramine, reductions in levels of LDL-C of 15.8% and 19.3% were seen with fluvastatin 10 mg and 20 mg, respectively. After an 8-week interval in which a daily dosage of cholestyramine 8 g was added, from baseline, reductions of 26.3% in the 10 mg fluvastatin-cholestyramine group and 31.2% in the 20 mg fluvastatin-cholestyramine group were observed, whereas the placebo-cholestyramine group displayed a reduction of 14.9%. Doubling the resin dosage to 16 g/day for the final 8 weeks of the study provided little additional benefit. Myotoxicity has been observed when lovastatin is coadministered with niacin, and so the combination of niacin with fluvastatin has also been studied to examine the possibility of this effect occurring. Patients were randomised to either fluvastatin 20 mg or placebo for 6 weeks, after which time open-label niacin was administered to all patients and titrated to a final dosage of 3 g/day. After 6 weeks, fluvastatin produced a 20.8% reduction in LDL-C levels from baseline. When combined with niacin, a 43.7% reduction was noted at the week 15 endpoint, against the 26.5% reduction seen with niacin monotherapy. The combination was well tolerated, with no reports of myopathy or of significant elevations in creatine kinase or liver transaminase levels. Combinations of fluvastatin with a variety of other agents have been shown to have significant effects on lipid profiles, with no evidence to date of clinically remarkable safety findings. Thus, the use of combination therapies may result in optimal management of patients with moderately severe hypercholesterolaemia and mixed dyslipidaemic profiles.
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PMID:Fluvastatin in combination with other lipid-lowering agents. 872 88


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