thromboxane-b2 and triflusal

Triflusal is an antiplatelet drug related to aspirin, with different pharmacological properties and a lower haemorrhagic risk. We aimed at comparing their effects on platelet and endothelial activation in type 2 diabetes mellitus (T2DM). In a randomized, double-blind, parallel group study, we compared the effects of three daily regimens (300, 600, and 900 mg) of triflusal, and aspirin (100mg/day) on urinary 11-dehydro-thromboxane (TX)B(2), index of in vivo platelet activation, ex vivo platelet function using the analyzer PFA-100, plasma von Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite and nitrate (NO(2)(-)+NO(3)(-)) in 60 T2DM patients. Triflusal induced a dose-dependent reduction in 11-dehydro-TXB(2) and a prolongation of closure time in the presence of collagen plus epinephrine (Coll/Epi-CT). The effects of the highest triflusal dose were not different from those of aspirin. The closure time in the presence of collagen plus ADP (Coll/ADP-CT), ICAM-1, VCAM-1, and NO(2)(-)+NO(3)(-) were not modified either by triflusal or aspirin. Plasma P-selectin and vWF were reduced by triflusal but not by aspirin. In T2DM triflusal causes a profound inhibition of platelet TXA(2) biosynthesis in vivo, acting on different targets involved in the platelet-endothelial cell interactions.

Topics: Adult; Aged; Aspirin; Biomarkers; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; P-Selectin; Platelet Activation; Platelet Aggregation Inhibitors; Radioimmunoassay; Retrospective Studies; Salicylates; Thromboxane B2; von Willebrand Factor

The aim of the study was to investigate the effects of the antiplatelet agent triflusal on the changes in platelet function in patients who underwent a cardiopulmonary bypass for coronary arteries (CABG). In 20 surgical patients, blood was sampled before and at the conclusion of surgery, 48 h later (in the intensive care unit), and after 10 days of treatment with 600 mg/day triflusal (triflusal was administered from the first day after surgery). Adenosine diphosphate (ADP) and collagen-induced platelet aggregation in whole blood, granular release of beta-thromboglobulin and platelet release of thromboxane B2 were measured. Basal values were compared with results in a group of ten healthy volunteers. All platelet determinations of activation were higher in coronary patients than in healthy volunteers. Immediately after CABG, the platelet reactivity to ADP and collagen were significantly lower, and release of beta-thromboglobulin and thromboxane B2 were higher, than in the pre-CABG samples. During the patient's stay in the intensive care unit, all values tend to return to pre-CABG values. Triflusal inhibits both platelet beta-thromboglobulin (63% with respect to the post-CABG value) and thromboxane B2 (91% with respect to the post-CABG value) release. Platelet aggregation after 10 days of triflusal treatment tended to return to the pre-CABG values. In conclusion, Triflusal reduces platelet activation caused by the coronary artery bypass graft surgery.

Topics: Adenosine Diphosphate; Adult; Aged; beta-Thromboglobulin; Collagen; Coronary Artery Bypass; Erythrocyte Count; Female; Hematocrit; Hemoglobins; Humans; Leukocyte Count; Male; Middle Aged; Myocardial Ischemia; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Salicylates; Thromboxane B2; Time Factors

The efficacy and safety of Triflusal capsules given to patients at thrombogenetic risk because of platelet hyperaggregation were investigated in a controlled study involving 15 patients (9 males and 6 females, mean age 65.7 years) who were given 300 mg/day of Triflusal during the first 5 days and 600 mg/day during the following 5 days. Subsequently, after 7 days of wash-out all these patients received placebo for 10 days, one capsule for the first 5 days and 2 capsules for the following 5 days. The platelet antiaggregant activity of the drug was evaluated by means of Born's platelet activation test. Specific tests were also made to assess the effect of this substance on platelet release and the coagulation system. The safety was evaluated by measuring the most important clinical chemistry and clinical haematology indexes of haematopoietic, hepatic, renal and metabolic functions. Arterial blood pressure and heart rate values were also recorded. All the 15 patients completed the study. It was found that the Triflusal treatment led to a significant mean reduction of the indexes chosen as markers of thrombophilia or platelet hyperaggregation in vivo. It did not affect the normal haemostatic-coagulation process and was well tolerated by the patients. The subsequent placebo treatment did not induce any platelet antiaggregant effects.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; beta-Thromboglobulin; Blood Platelet Disorders; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Factor 3; Platelet Factor 4; Salicylates; Thromboxane B2

1. Triflusal is a salicylic derivative that inhibits platelet aggregation in human whole blood with a minimal inhibition of prostacyclin production. 2. Aspirin inhibits platelet aggregation at concentrations that reduce vascular prostacyclin production.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Aspirin; Blood Platelets; Cyclooxygenase Inhibitors; Humans; In Vitro Techniques; Mesenteric Arteries; Muscle, Smooth, Vascular; Platelet Aggregation Inhibitors; Salicylates; Thromboxane B2

Triflusal (2-acetoxy-4-trifluormethylbenzoic acid) is a platelet-antiaggregant drug that selectively inhibits thromboxane synthesis with little effect on prostacyclin production. In this study, we evaluated the effect of 5-day administration of 900 mg/day triflusal on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary albumin excretion (UAE), thromboxane B2 (TXB2), 6-ketoprostaglandin F1 alpha (PGF1 alpha), and PGE2 in nine normotensive insulin-dependent diabetic patients with UAE between 30 and 103 micrograms/min. Plasma TXB2 and plasma renin activity (PRA) were also determined. After administration of triflusal, we observed a reduction in microalbuminuria (59 +/- 25 vs. 33 +/- 22 micrograms/min, P less than 0.01), an increase in RPF (648 +/- 119 vs. 722 +/- 134 ml.min-1 x 1.73 m-2, P less than 0.01), and a reduction in filtration fraction (0.24 +/- 0.04 vs. 0.20 +/- 0.03, P less than 0.01). Triflusal produced a significant reduction in both plasma TXB2 (130 +/- 39 vs. 52 +/- 32 pg/ml, P less than 0.02) and urine TXB2 (523 +/- 249 vs. 312 +/- 11 pg/min, P less than 0.02), without changes in PRA and UAE of 6-keto-PGF1 alpha and PGE2. Metabolic control and arterial blood pressure did not change during the study. These results suggest that platelet-antiaggregant therapy can reduce microalbuminuria in diabetic patients. This effect could be mediated by a reduction in the transglomerular hydraulic pressure through a vasodilation of efferent arterioles secondary to renal thromboxane synthesis inhibition.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Albuminuria; Blood Glucose; Diabetes Mellitus, Type 1; Dinoprostone; Female; Glomerular Filtration Rate; Humans; Male; Platelet Aggregation Inhibitors; Renal Circulation; Renin; Salicylates; Thromboxane B2

A study was made on the inhibitory effect of triflusal (600 mg/d X 15) and acetylsalicylic acid (ASA, 400 mg/d X 15) on platelet aggregation in whole blood (WB) and platelet-rich plasma (PRP) induced by ADP (2.5 mumol/l), adrenaline (50 mumol/l), collagen (1 microgram/ml) and arachidonic acid (0.8 mmol/l), in 30 insulin-dependent diabetic patients without vascular complications. Determination was also made of the serum levels of thromboxane B2 (TxB2) and of the plasma levels of 6-keto-PGF1-alpha and of beta-thromboglobulin (B-TG). Both drugs exhibited higher inhibitory effects in WB than in PRP. In WB, a significant difference between triflusal and ASA was observed against ADP-induced aggregation (67% and 46% inhibition respectively, p less than 0.01). Both drugs strongly inhibit the formation of TxB2 in serum (85% and 99%, respectively). Triflusal does not significantly change the plasma levels of 6-keto-PGF1-alpha; ASA, by contrast, causes reduction of over 95% in those plasma levels. The plasma levels of B-TG were not modified by either of the drugs.

Topics: Adult; Aspirin; beta-Thromboglobulin; Diabetes Mellitus, Type 1; Humans; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Prostaglandins F; Salicylates; Thromboxane B2

An in vitro and ex vivo study has been made to determine the inhibition of platelet aggregation in human whole blood (WB) and platelet rich plasma by triflusal and its main metabolite HTB (2-hydroxy-4-trifluoromethylbenzoic acid). Triflusal was administered orally at 300 mg x 2/day, for 15 days, to 13 healthy volunteers (ex vivo tests). Triflusal and HTB, at concentrations lower than 1 mM, produced a significant inhibition of platelet aggregation induced by ADP (2.5 microM, final) and collagen (1 microgram/ml, final) in PRP, while about 50% inhibition was induced in WB samples at 0.12 mM. Ex vivo studies also revealed a stronger inhibitory effect of triflusal in WB samples against several inducers; differences were particularly pronounced against ADP (10.6 times more potent in WB). These results suggest an important role of red blood cells and/or leukocytes in the mechanism of action of triflusal. The antiplatelet effect of triflusal in WB was modified when incubated with HTB at therapeutic concentrations. The IC50 value against collagen increased from 82 to 140 microM with 37.5 microM HTB, but decreased in a dose-dependent manner when incubated with higher concentrations of HTB, suggesting that inhibition of platelet cyclooxygenase by HTB masks its negative interaction with triflusal.

Topics: Adenosine Diphosphate; Adult; Collagen; Epinephrine; Humans; In Vitro Techniques; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Salicylates; Thromboxane B2