Laboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Lodz, Poland.
Students Research Group, Laboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Lodz, Poland.
Eur J Pharmacol. 2017 Sep 15;811:208-221. doi: 10.1016/j.ejphar.2017.06.011. Epub 2017 Jun 10.
Although metformin, an oral anti-diabetic drug, has been found to have multidirectional effects over the past decade, it is characterised by unfavourable pharmacokinetic properties. This study discusses the effects of metformin, phenformin and three prodrugs of metformin on the haemostasis and integrity of Red Blood Cells (RBCs). The influence of examined biguanide derivatives on haemostasis was evaluated spectrophotometrically by clot formation and lysis test (CL-test) at 405nm. The extrinsic and intrinsic coagulation pathway were examined by measuring the PT (Prothrombin Time) and aPTT (Activated Partial Tromboplastin Time). Haemolysis assay, microscopy and flow cytometry studies were used to assess the effect of the tested compounds on RBCs. Although none of the tested biguanide derivatives significantly influenced the overall potential of clot formation and fibrinolysis (CL constants), statistically significant changes were seen in the values of the kinetic parameters of fibrinolysis. Furthermore, only prodrug 2, with an 8-carbon alkyl chain, unfavourably affected RBCs by interaction with the erythrocyte membrane leading to significant haemolysis. Our results provide a further insight into the effects of metformin and its prodrugs on haemostasis and RBCs and underscore the necessity for further research.
尽管过去十年发现口服抗糖尿病药物二甲双胍具有多向作用，但它的药代动力学特性却不理想。本研究探讨了二甲双胍、苯乙双胍和二甲双胍的三种前药对血液凝固和红细胞（RBC）完整性的影响。通过在 405nm 处使用血凝块形成和溶解试验（CL 试验）分光光度法评估检查的双胍衍生物对止血的影响。通过测量 PT（凝血酶原时间）和 aPTT（活化部分凝血活酶时间）来检查外源性和内源性凝血途径。使用溶血试验、显微镜和流式细胞术研究来评估测试化合物对 RBC 的影响。尽管测试的双胍衍生物均未显着影响血凝块形成和纤维蛋白溶解的总体潜力（CL 常数），但纤维蛋白溶解的动力学参数值发生了统计学上的显着变化。此外，只有具有 8 个碳烷基链的前药 2 通过与红细胞膜相互作用不利地影响 RBC，导致显着的溶血。我们的研究结果进一步深入了解二甲双胍及其前药对血液凝固和 RBC 的影响，并强调需要进一步研究。
