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.

我们评估了ST抬高型心肌梗死（STEMI）患者在60 mg普拉格雷或180 mg替加格雷治疗后1h和24h CYP2C19和CYP3A4代谢活性对ADP诱导的血小板聚集的影响。此外，我们评估了CYP2C19多态性和药物对CYP酶活性的贡献。

STEMI患者被随机分配接受普拉格雷（n  = 51）或替卡格雷（n  = 46）治疗。CYP2C19和CYP3A4的代谢活性通过lansoprazole的5-羟基化和硫氧化反应速率进行评估。此外，对患者进行了CYP2C19 * 2和* 17等位基因的基因分型。

在接受普拉格雷治疗的患者中，负荷量后1h ADP诱导的高血小板反应性与5OH-兰索拉唑/兰索拉唑比率（r  = 0.44，p  = 0.002），CYP2C19代谢活性的标志物正相关，与兰索拉唑砜/兰索拉唑比率，反映CYP3A4的代谢活性（r = -0.35，p  = 0.018）。

CYP2C19弱代谢者具有较低的5OH-兰索拉唑/兰索拉唑比率和较高的兰索拉唑-砜/兰索拉唑比率，但对ADP诱导的血小板反应性无任何影响。用胺碘酮（一种CYP3A4抑制剂）的治疗既不影响代谢率也不影响ADP诱导的血小板反应性。

CYP3A4和CYP2C19代谢活性与普拉格雷治疗但替卡格雷治疗的STEMI患者与ADP诱导的血小板反应性相关。