Tran Quyen Thi, Baek In-Hwan, Han Na-Young, Yun Hwi-Yeol, Chae Jung-Woo
College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.
College of Pharmacy, Kyungsung University, Busan 48434, Korea.
Pharmaceutics. 2022 Jul 11;14(7):1446. doi: 10.3390/pharmaceutics14071446.
Propafenone (PPF) is a class 1C antiarrhythmic agent mainly metabolized by cytochrome (CYP) 2D6, CYP1A2, and CYP3A4. Previous studies have shown that CYP2D6 polymorphism influences the pharmacokinetics (PK) of PPF. However, the small sample sizes of PK studies can lead to less precise estimates of the PK parameters. Thus, this meta-analysis was performed to merge all current PK studies of PPF to determine the effects of the CYP2D6 phenotype more accurately on the PPF PK profile. We searched electronic databases for published studies to investigate the association between the PPF PK and CYP2D6 phenotype. Four PK-related outcomes were included: area under the time-concentration curve (AUC), maximum concentration (C), apparent clearance (CL/F), and half-life (t). A total of five studies were included in this meta-analysis ( = 56). Analyses were performed to compare PK parameters between poor metabolizers (PMs) versus extensive metabolizers (EMs). PPF has a non-linear pharmacokinetics; therefore, analyses were performed according to dose (300 mg and 400 mg). At 300 mg, the AUC mean (95% CI), C, and t of PPF in PMs were 15.9 (12.5-19.2) µg·h/mL, 1.10 (0.796-1.40) µg/mL, and 12.8 (11.3-14.3) h, respectively; these values were 2.4-, 11.2-, and 4.7-fold higher than those in the EM group, respectively. At 400 mg, a comparison was performed between S- and R-enantiomers. The CL/F was approximately 1.4-fold higher for the R-form compared with the S-form, which was a significant difference. This study demonstrated that CYP2D6 metabolizer status could significantly affect the PPF PK profile. Adjusting the dose of PPF according to CYP2D6 phenotype would help to avoid adverse effects and ensure treatment efficacy.
普罗帕酮（PPF）是一种1C类抗心律失常药物，主要由细胞色素（CYP）2D6、CYP1A2和CYP3A4代谢。先前的研究表明，CYP2D6基因多态性会影响PPF的药代动力学（PK）。然而，PK研究的样本量较小可能导致PK参数的估计不够精确。因此，进行了这项荟萃分析，以合并目前所有关于PPF的PK研究，从而更准确地确定CYP2D6表型对PPF PK曲线的影响。我们在电子数据库中搜索已发表的研究，以调查PPF PK与CYP2D6表型之间的关联。纳入了四个与PK相关的结果：时间-浓度曲线下面积（AUC）、最大浓度（C）、表观清除率（CL/F）和半衰期（t）。这项荟萃分析共纳入了五项研究（n = 56）。进行分析以比较慢代谢者（PMs）与快代谢者（EMs）之间的PK参数。PPF具有非线性药代动力学；因此，根据剂量（300 mg和400 mg）进行分析。在300 mg时，PMs中PPF的AUC均值（95%置信区间）、C和t分别为15.9（12.5 - 19.2）µg·h/mL、1.10（0.796 - 1.40）µg/mL和12.8（11.3 - 14.3）h；这些值分别比EM组高2.4倍、11.2倍和4.7倍。在400 mg时，对S-和R-对映体进行了比较。R型的CL/F比S型高约1.4倍，这是一个显著差异。本研究表明，CYP2D6代谢状态可显著影响PPF的PK曲线。根据CYP2D6表型调整PPF剂量将有助于避免不良反应并确保治疗效果。
