What is the pharmacokinetic profile of Ticagrelor (antiplatelet medication)?

From the Guidelines

Ticagrelor is a direct-acting oral P2Y12 receptor antagonist with a rapid onset of action, achieving peak inhibitory effects within 2 hours of a loading dose, and its pharmacokinetic properties support twice-daily dosing. The drug has a bioavailability of approximately 36% and is primarily metabolized by CYP3A4 enzymes, producing an active metabolite that contributes to its antiplatelet activity 1. Ticagrelor's half-life is around 7-9 hours, necessitating twice-daily dosing, typically 90mg twice daily after a 180mg loading dose 1. The drug and its metabolites are predominantly eliminated through hepatic metabolism and biliary excretion, with approximately 26% excreted in urine.

Key Points

• Ticagrelor demonstrates more consistent platelet inhibition than clopidogrel with less interindividual variability 1
• Its reversible binding to P2Y12 receptors allows for faster offset of action compared to other thienopyridines 1
• Dose adjustments are not required for renal impairment but caution is advised in severe hepatic impairment
• Concomitant use with strong CYP3A4 inhibitors or inducers should be avoided due to potential drug interactions that can significantly alter ticagrelor's plasma concentrations 1

Clinical Considerations

• The benefit of ticagrelor over clopidogrel was limited to patients taking 75 mg to 100 mg of aspirin 1
• The short half-life requires twice-daily administration, which could potentially result in adverse events in non-compliant patients, particularly after stent implantation
• When possible, ticagrelor should be discontinued at least 5 days before surgery 1

From the Research

Pharmacokinetic Properties of Ticagrelor

• Ticagrelor is an orally active, reversible, and selective adenosine diphosphate (ADP) receptor antagonist 2, 3, 4
• It has a faster onset of action and provides greater inhibition of platelet aggregation than clopidogrel 2, 3, 4
• Ticagrelor is effective in the treatment of patients with acute coronary syndromes (ACS), with or without ST-segment elevation 2, 3, 4

Comparison with Clopidogrel

• Ticagrelor was more effective than clopidogrel in reducing the incidence of the primary composite endpoint of myocardial infarction, stroke, or cardiovascular (CV) death 2, 3
• Ticagrelor reduced all-cause mortality relative to clopidogrel, although statistical significance of this was not confirmed in hierarchical testing 2
• The rate of death from any cause was also reduced with ticagrelor compared to clopidogrel 3

Safety and Tolerability

• Ticagrelor was generally well tolerated and was not associated with an increased risk of major bleeding relative to clopidogrel 2, 3
• However, the incidences of non-coronary artery bypass grafting (CABG)-related bleeding, and major or minor bleeding, as well as some non-hemorrhagic adverse events, including dyspnea and ventricular pauses, were higher with ticagrelor 2, 3, 5
• Ticagrelor significantly increased the rate of minor bleeding compared to clopidogrel 75mg daily during hospital and 6-month follow-up 6