目的:华法林与细胞色素P450(CYP)2C9抑制剂和诱导剂之间的药物-药物相互作用是众所周知的。很少有研究阐明CYP2C9抑制剂和诱导剂对华法林治疗的临床影响。这里,我们评估了CYP2C9介导的相互作用对华法林药效学的临床影响.
方法:这项回顾性观察研究纳入了2008年至2020年在Mie大学医院接受华法林治疗的患者。我们将凝血酶原时间-国际标准化比率/华法林每日剂量(PT-INR/剂量)定义为主要结局,并进行了多元线性回归分析以阐明影响主要结局的因素。此外,我们检查了接受CYP2C9诱导剂的患者的临床特征.
结果:在1,393名患者中,17人(1.2%)接受了卡马西平,利福平,苯巴比妥,或苯妥英钠作为CYP2C9诱导剂。多元线性回归分析表明,体重指数(BMI),血清白蛋白(Alb),估计肾小球滤过率(eGFR),CYP2C9诱导剂与PT-INR/剂量相关。多元回归方程如下:PT-INR/剂量=1.5900.004×年龄-0.020×BMI-0.141×Alb-0.001×eGFR-0.149×(如果同时使用CYP2C9诱导剂)(调整后的决定系数=0.106,Akaike信息标准=267.3,p<0.001)。在接受CYP2C9诱导剂的患者中,与CYP2C9抑制剂的共同给药无关,观察到较低的PT-INR/剂量值.
结论:除了年龄,BMI,Alb,和eGFR,调整华法林剂量和PT-INR时应考虑同时使用CYP2C9诱导剂.
OBJECTIVE: Drug-drug interactions between warfarin and cytochrome P450 (CYP) 2C9 inhibitors and inducers are well known. Few studies have clarified the clinical impact of CYP2C9 inhibitors and inducers on warfarin therapy. Here, we evaluated the clinical impact of CYP2C9-mediated interactions on the pharmacodynamics of warfarin.
METHODS: This retrospective observational
study enrolled patients who received warfarin between 2008 and 2020 at Mie University Hospital. We defined prothrombin time-international normalized ratio/daily warfarin dose (PT-INR/dose) as the primary outcome and conducted a multiple linear regression analysis to clarify the factors that affected the primary outcome. Additionally, we examined the clinical features of patients who received CYP2C9 inducers.
RESULTS: Out of 1,393 patients, 17 (1.2%) received carbamazepine, rifampicin, phenobarbital, or phenytoin as CYP2C9 inducers. Multiple linear regression analysis indicated that age, body mass index (BMI), serum albumin (Alb), estimated glomerular filtration rate (eGFR), and CYP2C9 inducers were associated with PT-INR/dose. The multiple regression equation was as follows: PT-INR/dose = 1.590 + 0.004 × age - 0.020 × BMI - 0.141 × Alb - 0.001 × eGFR - 0.149 × (if concomitant use of CYP2C9 inducers) (adjusted coefficient of determination = 0.106, Akaike information criterion = 267.3, p < 0.001). In patients receiving CYP2C9 inducers, lower PT-INR/dose values were observed regardless of co-administered CYP2C9 inhibitors.
CONCLUSIONS: In addition to age, BMI, Alb, and eGFR, concomitant use of CYP2C9 inducers should be considered when adjusting the warfarin dose and PT-INR.