Collett Savannah, Massmann Amanda, Petry Natasha J, Van Heukelom Joel, Schultz April, Hellwig Tadd, Baye Jordan F
Department of Pharmaceutical Services, Sanford USD Medical Center, Sioux Falls, SD 57117, USA.
Roger Maris Cancer Center, Sanford Medical Center, Fargo, ND 58102, USA.
J Pers Med. 2023 Feb 26;13(3):416. doi: 10.3390/jpm13030416.
Metoprolol is a medication commonly utilized in select patients to achieve a reduction in heart rate, systolic blood pressure, or other indications. A majority of metoprolol metabolism occurs via . Decreased expression of the CYP2D6 enzyme increases the concentration of metoprolol. Current pharmacogenomics guidelines by the Dutch Pharmacogenomics Working Group recommend slower titrations and dose decreases to minimize adverse effects from poor metabolizers or normal metabolizers taking concomitant medications that are strong inhibitors of CYP2D6 (phenoconverters). This study aimed to evaluate adverse effects such as bradycardia, hypotension, and syncope in patients who are expected to have absent CYP2D6 enzyme activity due to drug-drug or drug-gene interactions. The secondary aims of this study were to evaluate heart rate measurements for the included participants. Retrospective data were collected for individuals with genotyping results obtained for clinical purposes. Three categories (CYP2D6 normal metabolizers, poor metabolizers, and phenoconverters) were assigned. A total of 325 participants were included. There was no statistically significant difference found in the primary composite outcome between the three metabolizer groups ( = 0.054). However, a statistically significant difference was identified in the incidences of bradycardia between the poor metabolizers and the normal metabolizers or phenoconverters ( < 0.0001). The average heart rates were 2.8 beats per minute (bpm) and 2.6 bpm lower for the poor metabolizer and phenoconverter groups, respectively, compared to the normal metabolizers ( < 0.0001 for both comparisons). This study further supports the role of genetic testing in precision medicine to help individualize patient care as CYP2D6 poor metabolizers taking metoprolol were found to have an increase in bradycardia. Additional research is needed to clarify the dose relationship in this drug-gene interaction.
美托洛尔是一种常用于特定患者以降低心率、收缩压或用于其他适应症的药物。美托洛尔的大部分代谢通过……发生。细胞色素P450 2D6（CYP2D6）酶表达降低会增加美托洛尔的浓度。荷兰药物基因组学工作组当前的药物基因组学指南建议缓慢滴定并减少剂量，以尽量减少慢代谢者或服用CYP2D6强抑制剂（表型转化者）的正常代谢者因联合用药产生的不良反应。本研究旨在评估因药物 - 药物或药物 - 基因相互作用预计CYP2D6酶活性缺失的患者中诸如心动过缓、低血压和晕厥等不良反应。本研究的次要目的是评估纳入参与者的心率测量值。收集了因临床目的获得基因分型结果的个体的回顾性数据。分为三类（CYP2D6正常代谢者、慢代谢者和表型转化者）。共纳入325名参与者。在三个代谢者组之间的主要复合结局中未发现统计学显著差异（P = 0.054）。然而，在慢代谢者与正常代谢者或表型转化者之间的心动过缓发生率中发现了统计学显著差异（P < 0.0001）。与正常代谢者相比，慢代谢者组和表型转化者组的平均心率分别低2.8次/分钟（bpm）和2.6 bpm（两次比较P均< 0.0001）。本研究进一步支持基因检测在精准医学中的作用，以帮助实现个体化患者护理，因为发现服用美托洛尔的CYP2D6慢代谢者心动过缓增加。需要进一步研究以阐明这种药物 - 基因相互作用中的剂量关系。
