Thrombolytic agent — orbofiban
Very minor blood clot formation is part of the normal repair process in the vascular system, but in hypertension and vascular disease, larger areas of the endothelium may be damaged and so lead to the development of larger blood clots. Clots in the arterial circulation are more potentially dangerous and may cause life-threatening myocardial infarction. Clot formation is initiated by the aggregation of blood platelets at damaged sites, but conventional thrombolytic agents such as heparin are of little value against clots in the arterial system. In recent years, attention has been turned towards the development of inhibitors of blood platelet aggregation.
A key factor in this process is a glycoprotein receptor identifies as GPIIa/IIIb, which is an adhesive receptor on the platelet surface. The oldest inhibitor is aspirin, now used largely in small doses for prophylaxis, but a new and more potent inhibitor or antagonist of GPIIa/IIIb is the amidophenyl-pyrrolidino derivative orbofiban.1
Animal studies showed that orbofiban could inhibit collagen and adenosine phosphate-induced platelet aggregation,2 yet had no influence on the platelet count and caused no other changes in the haemotological profile. In studies in human subjects, it was found that the inhibition of platelet agggregation induced by orbofiban was dose-dependent, as was the effect of extending the bleeding time after orbofiban in doses of 20–785mg.3 In a randomised clinical trial in patients with myocardial infarction or unstable angina, orbofiban was given in daily doses of 30–50mg, together with aspirin, following which platelet aggregation time was reduced by 60–80%, with no increase in severe bleeding episodes.4 Other studies confirming the longer term safety and efficacy of the drug have also been reported.5