Ibrahim Areen, Odeh Mohanad, Mallah Eyad, Abu-Qatouseh Luay, Awaad Ahmad Abu, Ahmad Mohammad I A, Shdifat Amjad, Saleh Soadad, Al Hyari Muwafaq, Khadra Ibrahim, Omari Khaled W, Arafat Tawfiq
Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan.
Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, Jordan.
J Adv Pharm Technol Res. 2024 Jul-Sep;15(3):150-155. doi: 10.4103/JAPTR.JAPTR_99_24. Epub 2024 Jul 22.
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, = 0.011) and age (rs (87) =0.26, = 0.017). The homozygous (SULT1A1 genotype) correlation was moderate (rs (87) =0.21, = 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.
糖尿病是一种需要加以控制的常见疾病。药物治疗监测对于维持合适剂量非常有帮助。研究二甲双胍(在较小程度上还有格列美脲)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)工具测定药物浓度。开发了一种经过验证的LC-MS/MS方法来测定人血浆中的二甲双胍和格列美脲浓度。使用耶拿生物科学公司的血液DNA制备试剂盒进行DNA提取,其中使用柱式试剂盒提取用于基因多态性分析的DNA。在患有2型糖尿病的患者中,同时使用这两种药物并结合基因多态性进行研究。共评估了106名患者。SULT1A1纯合子和野生型CYP2D6 * 4的患病率分别为72.6%和73.6%。在对二甲双胍的每日摄入量进行校正后,五名二甲双胍血药浓度最高的患者中有三名没有纯合子(SULT1A1基因型)。从统计学角度来看,与二甲双胍血药浓度显示出不显著相关性变量的是体重指数(rs(87)=0.32,P = 0.011)和年龄(rs(87)=0.26,P = 0.017)。纯合子(SULT1A1基因型)相关性为中等(rs(87)=0.21,P = 0.052)。根据研究结果,CYP2D6基因型为wt/wt的患者的endoxifen水平明显高于v/v CYP2D6基因型的患者。该研究结果报告了二甲双胍(在较小程度上还有格列美脲)的血药浓度与基因分型(主要是SULT1A1基因型)之间可能存在的相关性。基因型指导的药物治疗可能为最大化药物疗效和/或最小化毒性提供新的贡献。