基因分析:糖尿病患者血浆中二甲双胍和格列美脲的治疗药物监测,包括基因多态性。

IF 1.4 Q3 Pharmacology, Toxicology and Pharmaceutics Journal of Advanced Pharmaceutical Technology & Research Pub Date : 2024-07-01 Epub Date: 2024-07-22 DOI:10.4103/JAPTR.JAPTR_99_24
Areen Ibrahim, Mohanad Odeh, Eyad Mallah, Luay Abu-Qatouseh, Ahmad Abu Awaad, Mohammad I A Ahmad, Amjad Shdifat, Soadad Saleh, Muwafaq Al Hyari, Ibrahim Khadra, Khaled W Omari, Tawfiq Arafat
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引用次数: 0

摘要

糖尿病是一种需要控制的广泛疾病。对药物进行治疗监测非常有助于维持理想剂量。研究二甲双胍(其次是格列美脲)的血药浓度与基因分型(主要是 SULT1A1 基因型)之间的相关性。使用经过验证的液相色谱-串联质谱(LC-MS/MS)工具确定药物水平。开发了一种经过验证的液相色谱-串联质谱(LC-MS/MS)方法,用于测定人体血浆中二甲双胍和格列美脲的含量。DNA 提取采用耶拿生物科学公司的血液 DNA 制备方法,其中的柱试剂盒用于提取 DNA 以进行基因多态性分析。在对 2 型糖尿病患者进行基因多态性研究的同时,还使用了这两种药物。共对 16 名患者进行了评估。SULT1A1 和野生型 CYP2D6 * 4 的同源性分别为 72.6% 和 73.6%。在对二甲双胍的日摄入量进行调整后,五名二甲双胍摄入量最高的患者中有三人没有同源性(SULT1A1 基因型)。据统计,与二甲双胍水平相关性不显著的变量是体重指数(rs (87) = 0.32,P = 0.011)和年龄(rs (87) = 0.26,P = 0.017)。同型(SULT1A1 基因型)相关性为中等(rs (87) =0.21,P =0.052)。研究结果表明,具有 wt/wt CYP2D6 基因型的患者体内的内奥昔芬含量大大高于具有 v/v CYP2D6 基因型的患者。研究结果表明,二甲双胍(其次是格列美脲)的血药浓度与基因分型(主要是 SULT1A1 基因型)之间可能存在相关性。基因型指导下的药物治疗可为最大限度地提高药物疗效和/或减少毒性做出新的贡献。
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Genetic analysis: Therapeutic drug monitoring of metformin and glimepiride on diabetic patients' plasma including genetic polymorphism.

Diabetes is a widespread disease that needs to be controlled. Therapeutic monitoring of drugs is very helpful in maintaining desirable doses. To study a correlation between the blood level of metformin (to a lesser extent, glimepiride) and genotyping (mainly the SULT1A1 genotype). Determine drug levels using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) tool. A validated LC-MS/MS method was developed to determine metformin and glimepiride levels in human plasma. DNA extraction was performed using Jena Bioscience's Blood DNA preparation, in which a column kit was used to extract DNA for genetic polymorphism. The investigation was carried out using both medications in type 2 diabetes patients alongside the genetic polymorphism. One hundred and six patients were assessed. The prevalence of homozygosity for SULT1A1 and wild-type CYP2D6 * 4 were 72.6% and 73.6%, respectively. After adjustment for daily intake of metformin, three patients out of five with the highest levels of metformin had no homozygosity (SULT1A1 genotype). Statistically, variables that demonstrated an insignificant correlation with the level of metformin were body mass index (rs (87) = 0.32, P = 0.011) and age (rs (87) =0.26, P = 0.017). The homozygous (SULT1A1 genotype) correlation was moderate (rs (87) =0.21, P = 0.052). According to the findings, patients with the wt/wt CYP2D6 genotype had considerably greater levels of endoxifen than those with the v/v CYP2D6 genotype. The study's results reported a probable correlation between the blood level of metformin (to a lesser extent, glimepiride) and genotyping (mainly the SULT1A1 genotype). Genotype-guided drug therapy may provide a novel contribution to maximize drug efficacy and/or minimize toxicity.

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来源期刊
CiteScore
2.00
自引率
7.10%
发文量
44
审稿时长
20 weeks
期刊介绍: Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is an Official Publication of Society of Pharmaceutical Education & Research™. It is an international journal published Quarterly. Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is available in online and print version. It is a peer reviewed journal aiming to communicate high quality original research work, reviews, short communications, case report, Ethics Forum, Education Forum and Letter to editor that contribute significantly to further the scientific knowledge related to the field of Pharmacy i.e. Pharmaceutics, Pharmacology, Pharmacognosy, Pharmaceutical Chemistry. Articles with timely interest and newer research concepts will be given more preference.
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