Evidence map›Paper›PMID 38637522›Full record

ArticleThe pharmacogenomics journal2024

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

Jianchang Qian, Tao Xu, Peipei Pan, Wei Sun, Guoxin Hu, Jianping Cai

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Article in The pharmacogenomics journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
4 · The record

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5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Jianchang QianInstitute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. qianjc@wmu.edu.cn.
Tao XuInstitute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Peipei PanTaizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.
Wei SunDepartment of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Guoxin HuInstitute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. hgx@wmu.edu.cn.ORCID 0000-0001-5169-4696
Jianping CaiInstitute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. caijp61@vip.sina.com.
Wenzhou Medical University · CNTaizhou Central Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 CYP2D6*1/*34 carriers are similar to those in CYP2D6*1/*1 carriers. However, in individuals carrying the CYP2D6*10/*87, CYP2D6*10/*95, and CYP2D6*97/*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, CYP2D6*1/*34 can be considered as normal metabolizers, while CYP2D6*10/*87, CYP2D6*10/*95, and CYP2D6*97/*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.

Indexed as

Adrenergic beta-AntagonistsMetoprololCytochrome P-450 CYP2D6GenotypeHumansPharmaceutical PreparationsPhenotypeAdrenergic beta-AntagonistsCytochrome P-450 CYP2D6MetoprololPharmaceutical Preparations

Identifiers

PMID38637522
OpenAlexW4394932997

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.