Fast, potent, and reliable inhibition of platelet aggregation
Clinica Medica, Università degli studi di Milano, Dipartimento di medicina chirurgia e odontoiatria, Ospedale San Paolo, via di Rudinì 8, 20145 Milano, Italy
* Corresponding author. Tel: +39 2503 23 095, Fax: +39 2503 23 090. E-mail address: marco.cattaneo{at}unimi.it
Thienopyridine inhibitors are administered as prodrugs and are metabolized to active compounds in the body by a range of enzymes including esterases and cytochrome P450s (CYPs). This review aims to characterize the main differences between the established drug clopidogrel and the newer agent prasugrel in terms of pharmacokinetics and how these differences relate to clinically relevant pharmacodynamic differences. Prasugrel is less dependent on CYP enzymes for its metabolism than clopidogrel. It is also more extensively metabolized to its active metabolite, which reaches higher plasma concentrations after dosing with a 60 mg loading dose or a 10 mg daily maintenance dose, relative to the licensed 300 mg/75 mg doses of clopidogrel. This higher pharmacokinetic exposure with prasugrel leads to significantly faster and more potent inhibition of platelet aggregation (IPA) than with clopidogrel. Prasugrel has also been shown to be associated with less variability of response than clopidogrel. This has been demonstrated by examining individuals’ responses in terms of IPA, and by assessing the degree of inhibition of the P2Y12 receptor—the site of action for both agents. These advantages with prasugrel vs. clopidogrel have been observed in healthy volunteers and in patients with coronary artery disease.
Key Words: Platelet aggregation • Thienopyridines • Prasugrel • Clopidogrel • Cytochrome P450