Study on genotype and phenotype of novel CYP2D6 variants using pharmacokinetic and pharmacodynamic models with metoprolol as a substrate drug

doi:10.1038/s41397-024-00332-3

科研成果详情

题名	Study on genotype and phenotype of novel CYP2D6 variants using pharmacokinetic and pharmacodynamic models with metoprolol as a substrate drug
作者	Qian, Jianchang1; Xu, Tao1; Pan, Peipei 2; Sun, Wei 3; Hu, Guoxin1; Cai, Jianping 1,4
发表日期	2024-06
发表期刊	The pharmacogenomics journal 影响因子和分区
语种	英语
原始文献类型	Journal Article
其他关键词	CONSORTIUM CPIC GUIDELINE
摘要	To investigate the pharmacokinetic and pharmacodynamic profiles of volunteers carrying CYP2D6 genotypes with unknow metabolic phenotypes, a total of 22 volunteers were recruited based on the sequencing results. Peripheral blood and urine samples were collected at specific time points after oral administration of metoprolol. A validated high-performance liquid chromatography (HPLC) method was used to determine the concentrations of metoprolol and α-hydroxymetoprolol. Blood pressure and electrocardiogram were also monitored. The results showed that the main pharmacokinetic parameters of metoprolol in CYP2D61/34 carriers are similar to those in CYP2D61/1 carriers. However, in individuals carrying the CYP2D610/87, CYP2D610/95, and CYP2D697/97 genotypes, the area under the curve (AUC) and half-life (t1/2) of metoprolol increased by 2-3 times compared to wild type. The urinary metabolic ratio of metoprolol in these genotypes is consistent with the trends observed in plasma samples. Therefore, CYP2D61/34 can be considered as normal metabolizers, while CYP2D610/87, CYP2D610/95, and CYP2D697/97 are intermediate metabolizers. Although the blood concentration of metoprolol has been found to correlate with CYP2D6 genotype, its blood pressure-lowering effect reaches maximum effectiveness at a reduction of 25 mmHg. Furthermore, P-Q interval prolongation and heart rate reduction are not positively correlated with metoprolol blood exposure. Based on the pharmacokinetic-pharmacodynamic model, this study clarified the properties of metoprolol in subjects with novel CYP2D6 genotypes and provided important fundamental data for the translational medicine of this substrate drug.
资助项目	National Natural Science Foundation of China[81973397];Natural Science Foundation of Zhejiang Province[LTGC23H310001];National Key Research and Development Program of China[2020YFC2008301];
出版者	SPRINGERNATURE
ISSN	1470-269X
EISSN	1473-1150
卷号	24 期号:3
DOI	10.1038/s41397-024-00332-3
页数	7
WOS类目	Genetics & Heredity ; Pharmacology & Pharmacy
WOS研究方向	Genetics & Heredity ; Pharmacology & Pharmacy
WOS记录号	WOS:001205105700001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	38637522
SCOPUSEID	2-s2.0-85190709663
通讯作者地址	[Qian, Jianchang]Institute of Molecular Toxicology and Pharmacology,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Hu, Guoxin]Institute of Molecular Toxicology and Pharmacology,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Cai, Jianping]Institute of Molecular Toxicology and Pharmacology,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Molecular Medicine;Genetics;Pharmacology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/211161
专题	药学院（分析测试中心）附属第二医院第二临床医学院、附属第二医院、育英儿童医院药学院（分析测试中心）_分子药理研究与教学中心
通讯作者	Qian, Jianchang; Hu, Guoxin; Cai, Jianping
作者单位	1.Institute of Molecular Toxicology and Pharmacology,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Taizhou Central Hospital (Taizhou University Hospital),Zhejiang,Taizhou,China; 3.Department of Pharmacy,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 4.The Key Laboratory of Geriatrics,Beijing Hospital & amp; Beijing Institute of Geriatrics,Ministry of Health,Beijing,100005,China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Qian, Jianchang,Xu, Tao,Pan, Peipei,et al. Study on genotype and phenotype of novel CYP2D6 variants using pharmacokinetic and pharmacodynamic models with metoprolol as a substrate drug[J]. The pharmacogenomics journal,2024,24(3).
APA	Qian, Jianchang, Xu, Tao, Pan, Peipei, Sun, Wei, Hu, Guoxin, & Cai, Jianping. (2024). Study on genotype and phenotype of novel CYP2D6 variants using pharmacokinetic and pharmacodynamic models with metoprolol as a substrate drug. The pharmacogenomics journal, 24(3).
MLA	Qian, Jianchang,et al."Study on genotype and phenotype of novel CYP2D6 variants using pharmacokinetic and pharmacodynamic models with metoprolol as a substrate drug".The pharmacogenomics journal 24.3(2024).