6-ketoprostaglandin-f1-alpha and triflusal

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

The biological effects of a new antiplatelet agent, triflusal, were evaluated in patients with cardiac valvular prostheses. Each patient received 900 mg/day of oral triflusal for 30 days. Triflusal significantly inhibited platelet aggregation induced by adenosine diphosphate (1 to 5 mumol) or epinephrine (12.5 mumol), showing a slight effect on bleeding time (basal: 6 +/- 1.7 min; 30 days of treatment: 8.0 +/- 2.7 min). Serum levels of thromboxane B2 were significantly reduced during treatment, but changes in serum levels of 6-keto-prostaglandin F1 alpha were not observed, suggesting that triflusal does not affect prostacyclin biosynthesis by the vascular wall. The results show that triflusal has a marked inhibitory and selective effect on platelet function in patients with cardiac valvular prostheses.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Count; Salicylates