Shihmanter R, Nulman I, Goland S, Caspi A, Bar-Haim A, Harary I, Berkovitch M, Arcavi L
Clinical Pharmacology Unit, Kaplan Medical Center, Hebrew University and Hadassah Medical School, Rehovot, Jerusalem, Israel.
J Clin Pharm Ther. 2014 Aug;39(4):432-8. doi: 10.1111/jcpt.12154. Epub 2014 Mar 27.
Carvedilol is the standard of care for heart failure (HF) patients. Carvedilol is partially metabolized by the highly polymorphic enzyme, CYP2D6. To reach an effective dose while avoiding adverse drug reactions (ADRs), testing of CYP2D6 genotype prior to carvedilol initiation may be considered. The objectives of this study were to determine CYP2D6 metabolic genotypes in an Israeli cohort of HF patients and to investigate the relationship between genotype, carvedilol dose and number of ADRs to determine the importance of CYP2D6 genotyping prior to treatment initiation.
Ninety-three patients with HF on carvedilol were CYP2D6 genotyped and classified as poor (PM), intermediate (IM), extensive (EM) or ultrarapid (UM) metabolizers. Carvedilol dose and ADRs were calculated and correlated with genotype using linear regression statistic analysis.
The distribution of the CYP2D6 phenotype in the Israeli population with HF is similar to the European general population. There were no significant differences of carvedilol dose and number of ADRs among genotype groups. Genotype group affiliation and number of adverse drug reactions were not predictive of carvedilol dose changes.
Genotype group affiliation and number of adverse drug reactions were not predictive of carvedilol dose during therapy for patients with HF. The Israeli CYP2D6 phenotype distribution in HF patients was consistent with the frequency in the general European population.
卡维地洛是心力衰竭（HF）患者的标准治疗药物。卡维地洛部分由具有高度多态性的细胞色素P450 2D6（CYP2D6）酶代谢。为了在避免药物不良反应（ADR）的同时达到有效剂量，可考虑在开始使用卡维地洛之前检测CYP2D6基因型。本研究的目的是确定以色列HF患者队列中的CYP2D6代谢基因型，并研究基因型、卡维地洛剂量与ADR数量之间的关系，以确定在开始治疗前进行CYP2D6基因分型的重要性。
对93例接受卡维地洛治疗的HF患者进行CYP2D6基因分型，并分为慢代谢型（PM）、中间代谢型（IM）、快代谢型（EM）或超快代谢型（UM）。使用线性回归统计分析计算卡维地洛剂量和ADR，并将其与基因型相关联。
以色列HF患者人群中CYP2D6表型的分布与欧洲普通人群相似。各基因型组之间的卡维地洛剂量和ADR数量没有显著差异。基因型组归属和药物不良反应数量不能预测卡维地洛剂量的变化。
对于HF患者，基因型组归属和药物不良反应数量不能预测治疗期间的卡维地洛剂量。以色列HF患者中CYP2D6表型分布与欧洲普通人群的频率一致。
