Disease relevance of K 3920

• Indobufen in the prevention of thromboembolic complications in patients with heart disease. A randomized, placebo-controlled, double-blind study [1].
• One hundred ninety-six patients with heart disease and at risk for cardiogenic embolism (90 with atrial fibrillation and 106 in sinus rhythm) were randomly assigned to receive indobufen (100 mg b.i.d.) or placebo [1].
• METHODS AND RESULTS: We randomized 20 patients (15 men and 5 women aged 59+/-10 years) with unstable angina to short-term treatment with aspirin (320 mg/d) or indobufen (200 mg BID) and collected 6 to 18 consecutive urine samples [2].
• Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models [3].
• Improvements in walking distances and microcirculatory parameters have been achieved during therapy with indobufen in patients with peripheral vascular disease and intermittent claudication [4].

High impact information on K 3920

• In vitro and ex vivo studies in healthy subjects demonstrated the capacity of indobufen to largely suppress monocyte PGHS-2 activity at therapeutic plasma concentrations [2].
• The purpose of this randomized, double-blind study was to evaluate the efficacy of indobufen, a reversible inhibitor of platelet cyclooxygenase, in the prevention of embolic events of cardiac origin [1].
• Adverse drug reactions, mostly gastrointestinal or hemostasis disorders, occurred in 9.2% of indobufen-treated patients [1].
• METHODS: A total of 916 patients with NRAF and a recent (< or = 15 days) cerebral ischemic episode were admitted to this multicenter, randomized study, during which they were treated with either indobufen (100 or 200 mg BID) or warfarin (to obtain an international normalized ratio of 2.0 to 3.5) for 12 months [5].
• RESULTS: Indobufen prevents TF expression and activity both in isolated and in whole blood monocytes [6].

Chemical compound and disease context of K 3920

• In order to prevent the development of thrombosis and other vascular complications, the drugs with antiaggregative effects were used (Ibustrin, Curantyl, Anopyrin) [7].
• OBJECTIVE: To examine the benefits and risks of long term anticoagulation (warfarin) compared with antiplatelet treatment (aspirin/indobufen) [corrected] in patients with non-rheumatic atrial fibrillation [8].
• Inhibition of thromboxane biosynthesis and platelet function by indobufen in type II diabetes mellitus [9].
• A comparative study between indobufen and acetylsalicylic acid on beta-thromboglobulin, platelet factor 4 and platelet aggregation in patients with transient ischemic attacks [10].
• Effects of indobufen and pentoxifylline on walking capacity and hemostasis in patients with intermittent claudication: results of six months of treatment [11].

Biological context of K 3920

• Indobufen is an inhibitor of platelet aggregation which acts by reversibly inhibiting the platelet cyclo-oxygenase enzyme [4].
• The d-enantiomer form of indobufen totally accounts for the anti-cyclooxygenase and antiplatelet activity ex vivo and for the increase in bleeding time by indobufen in man [12].
• 74 patients were randomized to treatment with indobufen (200 mg b.i.d.) and 76 patients to acenocoumarol (controlled by thrombotest) [13].
• Reduction of TxA2 synthesis, coupled with a lack of effect on PGE2 levels and prevention of ERK1/2 phosphorylation are highlighted as the mechanisms through which indobufen negatively affects TF [6].
• The plasma pharmacokinetics and urinary elimination of the enantiomers of indobufen (2-[p-(1-oxo-2-isoindolinyl)-phenyl]butyric acid), a novel platelet aggregation inhibitor, have been studied in male healthy volunteers given either the racemic compound or the S-enantiomer (200 mg racemate, 100 mg S-enantiomer) [14].

Anatomical context of K 3920

• Effects of antiplatelet therapy with indobufen or aspirin-dipyridamole on graft patency one year after coronary artery bypass grafting [15].
• Microthrombus formation on hemodialysis membranes: a placebo controlled randomized trail of two doses of Indobufen [16].
• We evaluated the effectiveness of indobufen administration in reducing neutrophil activation in a clinical model of ischemia-reperfusion [17].
• The racemic compound indobufen and its (+)- and (-)-enantiomers have been compared for their effects on blood platelet function and rat carrageenan pleurisy [18].
• In vitro and ex vivo effects of indobufen on red blood cell deformability [19].

Associations of K 3920 with other chemical compounds

• A small but statistically significant improvement in pain-free walking distance was determined by picotamide, indobufen, low molecular weight heparins, sulodexide and defibrotide, in small studies [20].
• The excretion balance and the urinary metabolism of indobufen (+/- 2-[p-(1-oxo-2-isoindolinyl)-phenyl] butyric acid), a platelet aggregation inhibitor, has been studied in rats and mice after oral administration [21].
• Racemic indobufen inhibits human platelet aggregation by reducing thromboxane (TX) A2 biosynthesis [22].
• In conclusion, indobufen is a selective inhibitor of the cyclooxygenase activity of platelet PGG/H synthase in a concentration range corresponding to the therapeutic plasma levels in man [22].
• The combined analysis showed that the difference in response frequency (indobufen compared with aspirin and dipyridamole) was close to 0: 2.0% (95% confidence interval (CI) -4.2 to 8.2) in terms of patients, and 0.8% (95% CI -2.5 to 4.2) in terms of distal anastomoses [23].

Gene context of K 3920

• Beta-thromboglobulin and platelet factor 4 plasma levels during haemodialysis: effect of indobufen [24].
• Pre-treatment with indobufen clearly inhibited beta-TG and PF 4 output [24].
• Reduction by indobufen of neutrophil activation in peripheral arterial occlusive disease [17].
• The ICD before treatment with indobufen or placebo averaged 137.9 +/- 68.2 and 136.6 +/- 63.2 m (mean +/- SD), respectively [25].
• The authors observed a decrease of platelet aggregation after treatment with indobufen and a decrease of F1 + 2 fragment and PAI-1 antigen after treatment with pentoxifylline [11].

Analytical, diagnostic and therapeutic context of K 3920

• Indobufen is well tolerated following oral administration and has been associated with a low incidence of adverse effects rarely requiring withdrawal of treatment [4].
• Enantiospecific analysis of indobufen in plasma and urine was achieved by HPLC of its L-leucinamide diastereoisomers [14].
• The role of Indobufen in preventing the formation of microthrombi on hemodialysis membranes has been investigated in 18 patients in a placebo controlled randomized double-blind cross-over study [16].
• In the secondary prevention of thromboembolic events indobufen 200 mg once or twice daily was significantly more effective than no treatment although not as effective as ticlopidine 250 mg once or twice daily, during 1-year nonblind clinical trials [26].
• A rapid and selective liquid chromatography (LC) with solid phase extraction (SPE) to quantify indobufen (INDB) enantiomers is described [27].

References