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

Abstract

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.

Thromboembolic complications after total hip replacement

“…INDO is an inhibitor of platelet aggregation blocking the conversion of arachidonic acid to cyclic endoperoxides [7,12]. Antiplatelet agents, particularly aspirin, are widely used in patients with cardiac, cerebral, and peripheral vascular disease [3,9], and also provide some positive effects in the prevention of DVT [4,10,18].…”

Indobufen inhibits tissue factor in human monocytes through a thromboxane-mediated mechanism

“…Indobufen is a reversible inhibitor of platelet cyclooxygenase (Cox) activity, and, as a consequence, it suppresses thromboxane A 2 (TxA 2 ) synthesis [1][2][3]. It is effective in a broad spectrum of prothrombotic conditions as graft occlusion after CABG surgery [4][5][6], restenosis after carotid endarterectomy [7], thromboembolic events in patients with heart disease [8], and intermittent claudication [9].…”

The (+)-enantiomer is responsible for the antiplatelet and anti-inflammatory activity of (±)-indobufen

“…Indobufen, ( )-2-(p-( 1 -oxo-2-isoindolinyl) -phenyl)-butyric acid, with a chiral centre in the 2 position of butyric acid, is a reversible inhibitor of cyclo-oxygenase. Its anti-aggregatory activity has been investigated in-vitro and in-vivo in the platelets of animals (Bergamaschi et a1 1979) and man (Fuccella et a1 1979;Vinazzer & Fuccella 1980;Cattaneo et al 1987;Pinto et a1 1987). As the enantiomers of the compound are available in pure form ( > 98%), we have compared the antiplatelet effects of (+)indobufen and its (+)-and (-)-enantiomers on human platelets in-vitro, by measuring the inhibition of serum thromboxane (Tx) Bz generation and platelet aggregation induced by different stimuli.…”