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他汀类药物相关药理学特征在糖尿病中的潜在改变。

Potential Alteration of Statin-Related Pharmacological Features in Diabetes Mellitus.

机构信息

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Weill Cornell Medicine Qatar, Doha, Qatar.

出版信息

Biomed Res Int. 2021 Mar 26;2021:6698743. doi: 10.1155/2021/6698743. eCollection 2021.

Abstract

OBJECTIVE

Type 2 diabetes mellitus is a chronic metabolic disease caused by insulin resistance or insulin deficiency resulting in elevated blood glucose levels. Poorly controlled diabetes is associated with the development of cardiovascular disease and dyslipidemia. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin) are an important class of therapeutic agents used to control hyperlipidemia and prevent cardiovascular disease in diabetic and nondiabetic patients. Since the effect of diabetes on the pharmacokinetics and pharmacodynamics of drugs and toxins has been shown, the aim was to review previous studies on the efficacy of statins such as atorvastatin, simvastatin, pravastatin, pitavastatin, fluvastatin, and rosuvastatin in clinical and preclinical studies in both diabetic and nondiabetic groups.

METHOD

For this purpose, Web of Science, PubMed, Scopus, and Google Scholar databases were reviewed, and related English articles published until October 2020 were included in this review article.

RESULTS

The findings revealed that diabetes affected statin effectiveness through changes in pharmacokinetic parameters such as clearance and biotransformation biomarkers at mRNA and protein levels. Plasma and serum concentrations of statins were accompanied by alteration in cellular activities including oxidative stress, Akt inhibition, and endothelial nitric oxide synthase (eNOS) and phosphorylation that were reflected in changes in the adverse drug reaction profile of the differing statins.

CONCLUSION

Given that dyslipidemia frequently accompanies diabetes and statin therapy is common, more clinical studies are needed regarding the effects of diabetes on the effectiveness of these drugs.

摘要

目的

2 型糖尿病是一种由胰岛素抵抗或胰岛素缺乏引起的慢性代谢性疾病,导致血糖水平升高。糖尿病控制不佳与心血管疾病和血脂异常的发展有关。3-羟基-3-甲基戊二酰辅酶 A(HMG-CoA)还原酶抑制剂(他汀类药物)是一类重要的治疗药物,用于控制糖尿病和非糖尿病患者的血脂异常和预防心血管疾病。由于已经证明糖尿病会影响药物和毒素的药代动力学和药效动力学,因此本研究旨在回顾之前关于阿托伐他汀、辛伐他汀、普伐他汀、匹伐他汀、氟伐他汀和瑞舒伐他汀等他汀类药物在糖尿病和非糖尿病患者的临床前和临床研究中的疗效的研究。

方法

为此,我们回顾了 Web of Science、PubMed、Scopus 和 Google Scholar 数据库,并纳入了截至 2020 年 10 月发表的相关英文文章。

结果

研究结果表明,糖尿病通过改变药代动力学参数(如清除率和生物转化标志物在 mRNA 和蛋白质水平上)影响他汀类药物的疗效。他汀类药物的血浆和血清浓度伴随着细胞活性的改变,包括氧化应激、Akt 抑制、内皮型一氧化氮合酶(eNOS)和磷酸化,这反映了不同他汀类药物不良反应谱的变化。

结论

鉴于血脂异常常伴有糖尿病,且他汀类药物治疗较为常见,因此需要更多的临床研究来探讨糖尿病对这些药物疗效的影响。

相似文献

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Risk of diabetes in patients treated with HMG-CoA reductase inhibitors.HMG-CoA 还原酶抑制剂治疗患者的糖尿病风险。
Metabolism. 2015 Apr;64(4):482-8. doi: 10.1016/j.metabol.2014.09.008. Epub 2014 Sep 28.

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