细胞色素P450 2D6基因多态性与美托洛尔和普罗帕酮联用的安全性

Cytochrome P4502D6 gene polymorphism and safety of combination use of metoprolol and propafenone

美托洛尔和普罗帕酮是心血管疾病常用药物。2药均通过肝脏细胞色素P450(CYP)2D6代谢,但普罗帕酮不仅是CYP2D6底物,也是CYP2D6抑制剂,与美托洛尔联用可能发生相互作用,导致不良反应发生。这种相互作用也取决于CYP2D6基因型。对于CYP2D6基因表型为慢代谢型(PM)和中间代谢型(IM)的患者,美托洛尔和普罗帕酮联用时可因普罗帕酮对CYP2D6的抑制而导致美托洛尔血药浓度升高。因此,应尽量避免美托洛尔与普罗帕酮联用。对于需要2药联合治疗的患者,用药期间应注意监测患者血压、心率、心电图变化,有条件者应检测CYP2D6基因型并根据检测结果调整药物剂量。

Metoprolol and propafenone are commonly used drugs in cardiovascular diseases.Both drugs are metabolized by liver cytochrome P450(CYP)2D6.However,propafenone is not only a CYP2D6 substrate,but also a CYP2D6 inhibitor,which may interact with metoprolol and cause adverse reactions.This interaction also depends on CYP2D6 genotype.For patients with CYP2D6 phenotypes of poor metabolizer(PM)and intermediate metabolizer(IM),the combination with propafenone can increase plasma concentration of metoprolol due to the inhibition of propafenone on CYP2D6.Therefore,the combination of metoprolol and propafenone should be avoided as far as possible.For the patients who need the combined treatment with the 2 drugs,attention should be paid to the monitoring of blood pressure,heart rate,and electrocardiogram changes during medication.If possible,CYP2D6 genotype should be detected and the drug dose should be adjusted according to the test results.