Abstract |
Platelet aggregation is the central process in the pathophysiology of acute coronary syndromes. ADP contributes to thrombosis by activating platelets, and AR-C69931MX is a specific antagonist of this process acting at the P2T receptor. At 5 hospitals, 39 patients with unstable angina or non-Q wave myocardial infarction, who were receiving aspirin and heparin, were administered intravenous AR-C69931MX with stepped dose increments over 3 h to a plateau of either 2 microg/kg/min for 21 h (Part 1; n = 12) or up to 69 h (Part 2; n = 13) or 4 microg/kg/min for up to 69 h (Part 3: n = 14). Safety parameters, platelet aggregation (PA) induced by ADP 3 micromol/L (impedance aggregometry), bleeding time (BT) and plasma concentrations of AR-C69931XX were assessed. AR-C69931MX was well tolerated. 33 patients completed the study. There were no deaths at 30 days and no serious adverse events attributed to AR-C69931MX. Trivial bleeding (56%) was common. At 24 h, mean inhibition of PA was 96.0 +/- 8.6, 94.9 +/- 14.4 and 98.7 +/- 2.1% and BT was 9.5 +/- 8.4, 14.0 +/- 9.7 and 16.0 +/- 11.1 min for Parts 1, 2 and 3 respectively. At 1 h post-infusion, mean inhibition of PA was 36.2 +/- 39.2, 20.7 +/- 25.9 and 40.7 +/- 36.7% respectively. 90% patients had a plasma half-life for AR-C69931XX of <9 min. In conclusion, AR-C69931MX is a potent, short-acting platelet ADP receptor antagonist suitable for further studies as an antithrombotic agent.
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Authors | R F Storey, K G Oldroyd, R G Wilcox |
Journal | Thrombosis and haemostasis
(Thromb Haemost)
Vol. 85
Issue 3
Pg. 401-7
(Mar 2001)
ISSN: 0340-6245 [Print] Germany |
PMID | 11307804
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial)
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Chemical References |
- Membrane Proteins
- P2RY12 protein, human
- Platelet Aggregation Inhibitors
- Purinergic P2 Receptor Antagonists
- Receptors, Purinergic P2Y12
- Adenosine Monophosphate
- cangrelor
- Heparin
- Aspirin
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Topics |
- Acute Disease
- Adenosine Monophosphate
(administration & dosage, analogs & derivatives, pharmacokinetics, standards)
- Adult
- Aged
- Angina, Unstable
(complications, drug therapy)
- Aspirin
(administration & dosage)
- Blood Coagulation Tests
- Consumer Product Safety
- Coronary Disease
(complications, drug therapy)
- Dose-Response Relationship, Drug
- Drug Therapy, Combination
- Electrocardiography
- Female
- Heparin
(administration & dosage)
- Humans
- Male
- Membrane Proteins
- Middle Aged
- Myocardial Infarction
(complications, drug therapy)
- Platelet Aggregation Inhibitors
(administration & dosage, pharmacokinetics, standards)
- Purinergic P2 Receptor Antagonists
- Receptors, Purinergic P2Y12
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