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

Heparin preparations have been used for prophylaxis and treatment of deep vein thrombosis for many years. Several biologic effects of heparin are known. Since 1978, there have been several reports about reversible elevation in serum values of AST and ALT in patients and healthy volunteers given heparin in small and high doses. Few studies report similar events in patients given LMW heparins. Results of two randomized studies (A and B) comprising 456 patients undergoing THR are presented. Two different compounds of LMW heparin (Logiparin or Enoxaparin) were used for thromboprophylaxis. Significant elevation during the postoperative period of AST and AP in study A, and AST, ALT, AP, LDH, and CK in study B were demonstrated in patients given LMW heparins in both studies. In study A the percentages of patients with normal preoperative values who reached pathologic values were 35% for AST and 15% for AP. In study B the percentages of patients with normal preoperative values who reached pathologic values were 36% for AST, 17% of ALT, 14% for AP, and 36% for LDH. The possible biologic mechanisms and the clinical perspectives are discussed. In all cases the changes in the liver enzymes returned to preoperative levels within 14 days.
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PMID:Biologic tolerance of two different low molecular weight heparins. 166 60

Eighty-two patients receiving long-term warfarin therapy provided 199.34 patient-years of data that were evaluated to determine if certain variables could identify those who might be monitored safely at less frequent intervals. Most patient demographics, social habits, medical histories, indications for anticoagulation, and concurrent therapy were not useful in discriminating between patients with stable (n = 67) and unstable (n = 15) anticoagulation. A few trends were noted, but they failed to achieve statistical significance. Patients who never achieved stability (the unstable group) tended to be younger than those who did (p 0.13). Among the stable patients, those with a diagnosis of deep vein thrombosis or pulmonary embolus, or with elevated alanine aminotransferase values, were significantly more likely to require a dosage change. The probability of requiring a dosage change at monthly visits did not correlate with the time required to become stable, but it did correlate inversely with the duration of stable anticoagulation. This probability declined from almost 16% when monitoring frequency was first extended to monthly intervals to less than 8% at 2 months of stable anticoagulation, and tended to decline further with longer periods of stable therapy. Of the 67 patients who became stable, 23 did not require a dosage change during an average of 526 days of follow-up. Among the 44 stable patients who required a dosage change, the mean time to the change was 250 days after becoming stable. Few complications occurred, almost all of them early in therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of factors associated with stability of anticoagulation therapy. 277 6

In 38 patients subjected to retropubic prostatectomy the effects of continuous lumbar epidural analgesia for 24 hours and the thiopentone- oxygen-nitrous oxide- alcuronium-pethidine sequence with artificial ventilation on the serum activities of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alpha-hydroxybutyrate dehydrogenase (HBD), and alkaline phosphatase (AP) have been studied. Per- and postoperative complications were recorded according to a prearranged plan designed to quantify the peroperative haemorrhage, postoperative deep vein thrombosis, pulmonary, circulatory and infectious complications. ASAT, ALAT and AP in the general group and ALAT in the epidural group showed significant increases on the 5th and 7th postoperative days. There existed no statistically significant difference between the groups. 82% of the patients with documented postoperative complications combined with hypoxaemia showed a pathologic liver enzyme pattern in contrast to 9% of the patients with uneventful postoperative course. It is concluded that the method of anaesthesia did not have an effect on the liver enzymes. Complications combined with postoperative hypoxaemia seemed to be the factors responsible for the increases of liver enzymes.
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PMID:Liver enzymes after retropubic prostatectomy in patients receiving continuous lumbar epidural analgesia or general anaesthesia. 618 33

A potential influence of idraparinux--a synthetic analogue of the pentasaccharide sequence in heparins--on plasma liver enzyme levels was analysed in 37 patients suffering from deep vein thrombosis and participating in the PERSIST trial. Plasma gamma-glutamyl-transferase, aspartate aminotransferase and alanine aminotransferase were determined prior to enoxaparin treatment (screening), prior to randomization (baseline) and once weekly during the 12-week treatment period. Patients were initially treated with weight-adjusted enoxaparin for 4-7 days and then randomized to either idraparinux (2.5, 5, 7.5 or 10 mg) or warfarin. Gamma-glutamyl-transferase was significantly increased after administration of enoxaparin at the baseline visit (P = 0.004) and in week 2 (P = 0.009) to return to screening levels in week 3 for the remaining study period (all P > 0.05). Aspartate aminotransferase (P = 0.001) and alanine aminotransferase (P < 0.001) were significantly increased at the baseline visit and returned to screening values at week 2 for the remaining study period (all P > 0.05). There was no significant difference between the mean values of plasma liver enzymes of the four idraparinux groups and the warfarin group in all 13 measurements. We concluded that idraparinux in contrast to enoxaparin does not increase plasma liver enzymes significantly.
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PMID:Idraparinux and liver enzymes: observations from the PERSIST trial. 1254 30

Melagatran is a synthetic, small-peptide direct thrombin inhibitor with anticoagulant activity. Ximelagatran, an oral prodrug, undergoes rapid enzymatic conversion to melagatran. Melagatran has rapid onset of action, fixed twice-daily dosing, stable absorption, apparent low potential for medication interactions, and no requirement for monitoring drug levels or dose adjustment. There is no specific antidote, but the drug has a short plasma elimination half-life (about 4 hours). In clinical studies, melagatran/ximelagatran is not inferior to warfarin for stroke prevention in patients with non-valvular atrial fibrillation, to heparin-warfarin for acute treatment and extended secondary prevention of deep vein thrombosis, and superior to warfarin for prevention of venous thromboembolism after major orthopaedic surgery. Major bleeding with melagatran/ximelagatran occurred at rates similar to those in patients treated with warfarin. 6%-12% of patients taking ximelagatran develop asymptomatic elevated liver enzyme levels (predominantly alanine aminotransferase) after 1-6 months of therapy; this usually resolves with cessation of therapy. Less than 1% of patients develop abnormal liver function while taking ximelagatran; this rarely persists or develops into clinical illness.
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PMID:The direct thrombin inhibitor melagatran/ximelagatran. 1574 44

Recently, ximelagatran and warfarin have been compared for stroke prevention in the Stroke Prevention using an Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) V trial in patients with non-valvular atrial fibrillation, and for the treatment of deep vein thrombosis in the Thrombin Inhibitor in Venous Thromboembolism (THRIVE) trial. In a mean follow-up of 20 months in SPORTIF V, the primary end point of stroke or systemic embolic events occurred in 37 patients in the warfarin group (of 1962) and 51 in the ximelagatran group (1960 patients). There was no difference between the groups in major bleeding. The rates of elevated alanine aminotransferase were much higher in the ximelagatran group (6%) than in the warfarin group (0.8%). In THRIVE, the primary efficacy end point of recurrent venous thromboembolism occurred in 26/1240 ximelagatran patients and 24/1249 patients in the enoxaparin/warfarin group. The incidence of alanine aminotransferase levels greater than three times the upper limit of normal was much higher with ximelagatran than with enoxaparin/warfarin (9.6 and 2.0%, respectively). In conclusion, although the trials comparing ximelagatran with warfarin as prophylaxis for stroke in atrial fibrillation and in the treatment of venous thromboembolism show noninferiority, concerns about the hepatic safety of ximelagatran remain.
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PMID:Ximelagatran--recent comparisons with warfarin. 1614 13

Despite the significant advances over the last 50 years with regard to anticoagulant therapy, warfarin remains the definitive standard for the long-term prevention of thromboembolic events in at-risk patients, except those with acute coronary syndromes, in which antiplatelets are preferred. Ximelagatran, a prodrug of melagatran, is an orally administered direct thrombin inhibitor whose therapeutic potential has been investigated in venous thromboembolism, acute coronary syndromes and prevention of stroke in atrial fibrillation. Clinical studies have demonstrated ximelagatran to be comparable in efficacy to the oral vitamin K antagonist warfarin and low molecular weight heparin for prophylaxis of venous thromboembolism, comparable to warfarin for stroke prevention in the setting of atrial fibrillation, and, when combined with aspirin, more effective than aspirin alone at preventing major adverse cardiovascular events in patients with a recent myocardial infarction. Double-blind trials have also revealed the efficacy of ximelagatran in the secondary prevention of venous thromboembolism and shown the agent to be as effective as enoxaparin/warfarin in treating patients with acute deep vein thrombosis. Adverse effects with ximelagatran include elevations in alanine transaminase (ALT), which may require monitoring, and bleeding complications. Bleeding complications appear to be less than or at least comparable to those occurring with standard anticoagulant treatments like warfarin or low molecular weight heparin. In addition to its favorable efficacy and safety profile in comparison with standard anticoagulant therapy, the convenience of its oral, fixed-dose administration without the need for anticoagulation monitoring might help encourage a wider use of appropriate anticoagulation using ximelagatran across the population at risk, reducing the incidence of thromboembolic events.
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PMID:Ximelagatran. 1651 7

In patients with acute pulmonary embolism (PE) the frequency of deep vein thrombosis (DVT) varies between 13-93%. The aim of this study was to compare Doppler ultrasonography (DUSG) and venography in the detection of DVT in patients with PE. Fifty-one patients who were clinically diagnosed as having PE from January 1st 2001 to January 31st 2005 were entered into the study and comorbid conditions and risk factors were noted. The diagnosis of PE was confirmed by ventilation-perfusion (V/Q) scintigraphy, spiral tomography and angiotomography while the diagnosis of DVT was made by DUSG and venography. DVT was confirmed by both DUSG and venography in 19 (37,3%) patients. In the remaining 32 patients DUSG was negative. Venography confirmed DVT in 6 of these patients while in 26 no DVT was found. The sensitivity and specifity of DUSG in the diagnosis of DVT were 76% and 100% respectively and the negative and positive predictive values were 81% and 100% respectively. The mean d-dimer concentration was 1,187 in patients with DVT and 641 in patients without DVT (p > 0.05). Aquired risk factors were found in 4 of 6 patients with DVT, CRP was elevated in 5 (83%) and ALT-AST were elevated in 2 (33%). Although DUSG alone is considered sufficient for the diagnosis of DVT, venography still remains the gold standard in the diagnosis of DVT. Especially in patients with PE, where the diagnosis of DVT may increase the success of treatment, venography or other diagnostic tools may be used instead of a second DUSG if the first DUSG is negative.
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PMID:Doppler ultrasonography versus venography in the detection of deep vein thrombosis in patients with pulmonary embolism. 1795 43

The treatment of acute venous thromboembolism and prophylaxis of recurrent events with heparin/low molecular weight heparin followed by vitamin K antagonists is limited by several factors. Oral direct thrombin inhibitors (ODTIs) showed a better pharmacological activity and might be an alternative in the treatment of venous thromboembolism. The Thrombin Inhibition in Venous Thromboembolism (THRIVE) program performed some studies developing the ODTI ximelagatran for this indication, and it is presented in the overview. The aim of the THRIVE I study was the dose finding, and that of the THRIVE IV study the applicability in hemodynamic stabile pulmonary embolism. A prospective, randomized, double blind trial was performed to compare oral ximelagatran with enoxaparin/warfarin for a 6-month treatment of acute venous thrombosis (THRIVE II and V). A second double blind study compared ximelagatran with placebo over 18 months after a 6-month anticoagulant therapy of acute deep vein thrombosis. The efficacy and safety of treatment of patients with acute deep venous thrombosis who received 2 infinity 36 mg ximelagatran was not inferior to that of patients who received a conventional anticoagulant for prophylaxis of recurrent events over 6 months. Ximelagatran 2 infinity 24 mg significantly reduced recurrent thromboembolic events compared to placebo without increasing the risk for hemorrhage. A reversible symptomless increase of alanine aminotransferase occurs in 6% to 9.6% of patients between months 2 and 4. The results of the follow-up studies suggest that thromboembolic events may recur in patients with acute venous thromboembolism after termination of treatment with both vitamin K antagonists and ximelagatran.
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PMID:Ximelagatran for treatment and prophylaxis of recurrent events in deep vein thrombosis. 1763 92

Sequential chemotherapy may improve treatment efficacy avoiding the additive toxicity associated with concomitant polichemotherapy in hormone-refractory prostate cancer (HRPC). Forty patients received docetaxel 30 mg m(-2) intravenous (i.v.), weekly, plus estramustine 280 mg twice daily for 12 weeks. After 2 weeks rest, patients with a decline or stable PSA were treated with mitoxantrone 12 mg m(-2) i.v. every 3 weeks plus prednisone 5 mg twice daily for 12 cycles. Forty patients were assessable for toxicity after docetaxel/estramustine. Main toxicities were grade 3-4 AST/ALT or bilirubin increase in seven patients (17.5%) and deep venous thrombosis (DVT) in four patients (10%). Twenty-seven patients received mitoxantrone/prednisone. Main toxicities included DVT in one patient (3.7%) and congestive heart failure in two patients (7%). Thirty-nine patients were assessable for PSA response. Twenty-nine patients (72.5%; 95% CI 63-82%) obtained a >/=50% PSA decline with 15 patients (37.5%; 95% CI 20-50%) that demonstrated a >/=90% decrease. Median progression-free and overall survival were respectively 7.0 (95% CI 5.8-8.2 months) and 19.2 months (95% CI 13.9-24.3 months). In conclusion, although this regimen demonstrated a favourable toxicity profile, sequential administration of mitoxantrone is not able to improve docetaxel activity in patients with HRPC.
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PMID:Phase II study of sequential chemotherapy with docetaxel-estramustine followed by mitoxantrone-prednisone in patients with advanced hormone-refractory prostate cancer. 1802 96


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