摘要:

The purpose of this manuscript is to review the available antagonists of platelet glycoprotein (GP) IIb/IIIa. The critical role of platelet aggregation in the pathogenesis of acute coronary syndromes of unstable angina and non-Q-wave myocardial infarction, as well as in mediating abrupt vessel closure and periprocedural infarction after percutaneous coronary interventions, has been recognised recently. Platelet aggregation is mediated through expression of activated GP IIb/IIIa and its subsequent binding to circulating fibrinogen. Inhibition of this interaction with one of 3 commercially available agents has been demonstrated to reduce ischaemic complications of coronary intervention and to reduce the rates of death and myocardial infarction in patients with acute coronary syndromes. Differential pharmacological characteristics of the drugs abciximab, tirofiban and eptifibatide are described and the trials which have defined their role in the management of ischaemic heart disease are reviewed.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All the drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for a full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&D InsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;FK 633 (FR 144633) is a glycoprotein IIb/IIIa receptor antagonist undergoing development with Fujisawa in Japan. It is in phase II trials for thrombosis and under preclinical development for the treatment of restenosis.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Fradafiban (BIBU 52, BIBU 52 ZW) is a nonpeptide fibrinogen antagonist that is undergoing phase I/IIa trials with Boehringer Ingelheim Pharma KG in Europe. The orally active prodrug of fradafiban is lefradafiban. Other compounds in the same series of nonpeptide fibrinogen antagonists include BIBW 98.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Lamifiban (RO 449883), a platelet glycoprotein IIb/IIIa receptor antagonist, is being developed by Roche. It is undergoing phase III clinical trials worldwide for the treatment of acute coronary syndromes, including unstable angina pectoris and non-Q-wave myocardial infarction. Lamifiban is also in phase II trials in Japan. Following from the PARAGONA and PARADIGM studies, the worldwide PARAGON B trial in patients with unstable angina pectoris and non-Q-wave myocardial infarction is underway. The trial will include 4000 patients and the dose will be individualised according to the patient's renal function.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Lefradafiban (BIBU 104, BIBU 104XX) is an oral prodrug of fradafiban, the active glycoprotein IIb/IIIa receptor antagonist. It is currently undergoing phase II clinical development with Boehringer Ingelheim Pharma KG in Germany for use as an oral antithrombotic agent. Results from a dose-finding study were presented at the European Society of Cardiology meeting in Stockholm August 1997, and further studies using the lower doses are planned.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Roxifiban (DMP 754, MK 0853, XJ 754) is the lead compound from a series of isoxazolines, non-peptide glycoprotein IIb/IIIa antagonists that are orally active. Roxifiban is the monoacetate prodrug and its active free acid form is XV 459. Roxifiban is an analogue of XR 300, with increased antiplatelet activity and duration of action. It has demonstrated potent and selective antiplatelet activityin vitroand is under phase II clinical development with DuPont Pharmaceuticals (formerly DuPont Merck) in the US for the treatment of thrombotic disorders. A study in aspirin treated patients undergoing coronary angioplasty is underway.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Sibrafiban (RO 483657, RO 483657-001, XubixTM) is a double oral prodrug that undergoes conversion to the inactive prodrug RO 483656, which in turn is metabolised to the potent, nonpeptide glycoprotein IIb/IIIa receptor antagonist RO 443888. Sibrafiban appears to be well tolerated in animals and produces dose-dependent effects on platelet aggregation and template bleeding times.Sibrafiban is under development with Roche, while Genentech has retained option rights for the product. It is being developed worldwide for the prevention of secondary events in patients following acute coronary syndromes, including unstable angina pectoris or myocardial infarction. A phase III study (the SYMPHONY trial) is being conducted worldwide in 9000 patients stabilised after a myocardial infarction or unstable angina pectoris. A twice daily dosage regimen is to be used. A long term study (2nd SYMPHONY) is also underway and will continue for a minimum duration of 12 months and recruit about 8400 patients. The dosages used in both studies were determined in the TIMI 12 study and achieve plasma RO 443888 levels of between 7 and 40 &mgr;g/L.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;TP 9201, a synthetic RGD-containing cyclic peptide, is a glycoprotein IIb/IIIa receptor antagonist which has undergone phase I trials in the US as an antithrombotic agent for the treatment of thromboses associated with acute unstable angina pectoris, restenosis, reocclusion, ischaemic stroke, and reperfusion injury resulting from vascular grafts, reconstructive surgery and organ transplantation. Telios Pharmaceuticals (Integra LifeSciences) and Genentech were originally collaborating on the development of TP 9201, but in October 1992 Telios acquired the worldwide rights to TP 9201. TP 9201 is available for licensing worldwide.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS