Platelet Release Reaction and Prostaglandin Pathway Activation in Angina Patients during Exercise: Effect of Indobufen

Pogliani, E; Fantasia, R; Savino, Rocco; Montani, Maura

doi:10.1177/030006058301100102

Cited by 4 publications

(1 citation statement)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indobufen also inhibits the production of malondialdehyde [14,16] and thromboxane B2 (TxB2) [ 1,14] by platelets stimulated with thrombin. On the basis of the cumulative analysis of these data it has been suggested that indo bufen inhibits platelet aggregation by inter fering with the arachidonate pathway, possi bly at the cyclooxygenase level.…”

Section: Introductionmentioning

confidence: 99%

In vitro and ex vivo Effects of Indobufen on Human Platelet Aggregation, the Release Reaction and Thromboxane B2 Production

Cattaneo¹,

Bevilacqua²,

Lecchi³

et al. 1987

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

We have done a comprehensive study in normal volunteers of the in vitro and ex vivo effects of the antiplatelet agent indobufen on platelet aggregation, the release reaction and thromboxane B₂ (TxB₂) production as induced by different concentrations of aggregating agents. At low concentrations (10 μM), indobufen completely inhibited secondary platelet aggregation, the release reaction and TxB₂ production stimulated by ADP, epinephrine and low concentrations of platelet-activating factor (PAF acether). Higher concentrations of indobufen (100 μM) completely inhibited TxB₂ production, platelet aggregation and ATP release induced by arachidonic acid (1 mM) or collagen (2 μg/ml). The inhibitory effect was partially overcome by higher concentrations of arachidonic acid (2 mM). Data obtained ex vivo 2 h after the oral administration of 200 mg indobufen to 8 normal volunteers were in keeping with those of the in vitro study. We conclude that indobufen inhibits platelet aggregation and the release reaction by inhibiting the platelet arachidonate pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

In vitro and ex vivo Effects of Indobufen on Human Platelet Aggregation, the Release Reaction and Thromboxane B2 Production

Cattaneo¹,

Bevilacqua²,

Lecchi³

et al. 1987

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

show abstract

Inhibition of thromboxane biosynthesis and platelet function by indobufen in type II diabetes mellitus.

Davı̀

Patrono

Catalano

et al. 1993

Arterioscler Thromb

View full text Add to dashboard Cite

Indobufen is a reversible inhibitor of platelet prostaglandin G/H-synthase. To verify the dose dependence of the antiplatelet effect of indobufen on ex vivo and in vivo indexes of thromboxane (TX) biosynthesis and TXAj-dependent platelet function, we studied nine patients with non-insulin-dependent diabetes mellitus (NIDDM). This was a randomized, double-blind, crossover study in which each patient was treated with three different daily regimens (50 rag BID, 100 mg BID, and 200 mg BID) of indobufen for 1 week, with a 7-day washout period between treatments. Urinary 11-dehydro-TXBj excretion averaged 58.2±21.8 ng/h at baseline. TX metabolite excretion was reduced dose dependently by indobufen: by 67% at 50 mg BID, 72% at 100 mg BID, and 81% at 200 mg BID. Platelet cyclooxygenase activity, ATP release, collageninduced platelet aggregation, and bleeding time also were modified dose dependently by indobufen. Biochemical demonstration of suppressed platelet TX A 2 in vivo was accompanied by evidence of inhibited platelet function as assessed ex vivo. Under pathophysiological conditions, such as NIDDM, which are associated with enhanced TX A 2 synthesis, more than 95% suppression of platelet cyclooxygenase activity may be necessary to produce virtually maximal inhibition of platelet TXA 2 biosynthesis in vivo. The inhibitor effect of the racemic mixture can be largely accounted for by the action of the S-isomer. 2Indobufen currently is used as an antithrombotic agent at a dosing regimen of 200 mg BID. At this dose, its antithrombotic effect is comparable to that of aspirin (325 mg TID) plus dipyridamole (75 mg TID) in preventing graft occlusion after coronary artery bypass surgery.3 Dose-ranging studies with indobufen were largely based on capacity-related measurements of platelet function ex vivo. 4 -7 Because the latter do not necessarily reflect the extent of platelet inhibition in vivo, we set out to explore the dose dependence of the antiplatelet effect of indobufen through ex vivo and in vivo measurements of thromboxane (TX) biosynthesis and TX A 2 -dependent platelet function. We performed a double-blind, crossover study in patients with non-insulin-dependent diabetes mellitus (NIDDM) with macrovascular complications because of previous evidence for enhanced TX A 2 biosynthesis in this setting.

show abstract

Indobufen

Bhana¹,

McClellan²

2001

Drugs & Aging

View full text Add to dashboard Cite

Indobufen is as effective as warfarin in the prophylaxis of thromboembolic events in at risk patients with nonrheumatic atrial fibrillation, as aspirin plus dipyridamole in the prevention of CABG occlusion and may be more effective than aspirin or pentoxifylline in improving walking capacity in patients with intermittent claudication. The improved tolerability profile of indobufen (favourable gastric tolerance and reduced haemorrhagic complications) compared with aspirin 300 to 325 mg 3 times daily or warfarin, in addition to a similar antiplatelet effect, suggests indobufen can be considered a drug with a definite role in the management of atherothrombotic events. In particular, indobufen may be an effective alternative for at risk patients with nonrheumatic atrial fibrillation in whom anticoagulant therapy is contraindicated or who are at higher risk of bleeding.

show abstract

Platelet Release Reaction and Prostaglandin Pathway Activation in Angina Patients during Exercise: Effect of Indobufen

Cited by 4 publications

References 15 publications

In vitro and ex vivo Effects of Indobufen on Human Platelet Aggregation, the Release Reaction and Thromboxane B2 Production

In vitro and ex vivo Effects of Indobufen on Human Platelet Aggregation, the Release Reaction and Thromboxane B2 Production

Inhibition of thromboxane biosynthesis and platelet function by indobufen in type II diabetes mellitus.

Indobufen

Contact Info

Product

Resources

About