CYP2C19 and CYP3A4 activity and ADP-induced platelet reactivity in prasugrel- or ticagrelor-treated STEMI patients: monocentric study in PRAGUE-18 trial participants

• Published in: Xenobiotica 2020-08, Vol.50 (8), p.929-938
• Main Authors: Máchal, J., Hlinomaz, O., Kostolanská, K., Peš, O., Máchalová, A., Šplíchal, Z., Mot'ovská, Z., Juřica, J.
• Format: Article
• Language: English
• Subjects: ADP test; aggregation; Cytochrome P450; lansoprazole; prasugrel; ticagrelor
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498254.2020.1731625

We assessed the contribution of CYP2C19 and CYP3A4 metabolic activity to the ADP-induced platelet aggregation 1h and 24h after a loading dose of 60 mg prasugrel or 180 mg ticagrelor in patients with ST-elevation myocardial infarction (STEMI). Further, we assessed the contribution of CYP2C19 polymorphisms and medication to the CYP enzymatic activity. Patients with STEMI were randomly assigned to the treatment with prasugrel (n = 51) or ticagrelor (n = 46). Metabolic activity of CYP2C19 and CYP3A4 was assessed by the rate of 5-hydroxylation and sulfoxidation of lansoprazole. Further, patients were genotyped for CYP2C19 *2 and *17 alleles. In prasugrel-treated patients, high ADP-induced platelet reactivity 1h after the loading dose positively correlated with 5OH-lansoprazole/lansoprazole ratio (r = 0.44, p = 0.002), a marker of CYP2C19 metabolic activity, and negatively with lansoprazole-sulfone/lansoprazole ratio, which reflects CYP3A4 metabolic activity (r = −0.35, p = 0.018). CYP2C19 poor metabolizers had lower 5OH-lansoprazole/lansoprazole ratio and higher lansoprazole-sulfone/lansoprazole ratio, but without any effect on the ADP-induced platelet reactivity. The treatment with amiodarone, a CYP3A4 inhibitor, influenced neither the metabolic ratios nor the ADP-induced platelet reactivity. The CYP3A4 and CYP2C19 metabolic activity is associated with ADP-induced platelet reactivity in prasugrel-treated, but not ticagrelor-treated patients with STEMI.