As the pharmacokinetic properties of metformin are unfavourable, several analogues and prodrugs have been synthesised to improve its bioavailability. The aim of this study was to assess the plasma stability of sulfenamide and sulfonamide derivatives of metformin and establish their effects on plasma haemostasis and integrity of red blood cells (RBCs).

The overall haemostasis potential was evaluated spectrophotometrically by clot formation and lysis test (CL-test). PT (Prothrombin Time) and APTT (Activated Partial Tromboplastin Time) were used to evaluate the effects if the compounds on the extrinsic and intrinsic coagulation pathway. Haemolysis assay, microscopy and flow cytometry studies were conducted to determine the effect of the compounds on RBCs.

Two sulfonamide and one sulfenamide derivatives of metformin were associated with a statistically significant decrease in the overall potential of clot formation and fibrinolysis (↓ CL_AUC), suggesting that these compounds may exert beneficial effects regarding plasma haemostasis, which is frequently impaired in diabetic patients. p- and o-Nitrobenzene sulfonamides contributed to the beneficial change in kinetic parameters of clot formation and fibrinolysis. o-Nitrobenzene sulfonamide significantly increased thrombin generation time (↑ TGt) and was also found to prolong both APTT and PT. All compounds did not exert any effects on the integrity of RBCs over the concentration range 0.006–0.6 μmol/mL which constitutes the expected therapeutic concentration.

In conclusion, sulfonamide derivatives of metformin present potentially beneficial properties in terms of plasma haemostasis which is frequently impaired in T2DM patients. Therefore, metformin sulfonamides may become a prototype for further design and synthesis of novel metformin analogues and prodrugs with improved pharmacokinetic properties.

由于二甲双胍的药代动力学特性不佳，因此已合成了几种类似物和前药以改善其生物利用度。这项研究的目的是评估二甲双胍的次磺酰胺和磺酰胺衍生物的血浆稳定性，并确定它们对血浆止血和红细胞完整性的影响。

通过血凝块形成和裂解测试（CL测试）以分光光度法评估了总体止血潜力。PT（凝血酶原时间）和APTT（活化的部分促凝血酶原时间）用于评估化合物是否对外部和固有凝​​血途径产生影响。进行了溶血测定，显微镜检查和流式细胞术研究，以确定化合物对红细胞的作用。

二甲双胍的两种磺酰胺和一种磺酰胺衍生物与血凝块形成和纤维蛋白溶解（↓CL _AUC）的总体潜力在统计学上显着降低有关，表明这些化合物可能对血浆止血产生有益作用，而糖尿病止血经常被削弱。对和邻硝基苯磺酰胺有助于血凝块形成和纤维蛋白溶解动力学参数的有益变化。Ø-硝基苯磺酰胺显着增加了凝血酶的生成时间（↑TGt），并且还发现可以延长APTT和PT的时间。在构成预期治疗浓度的0.006-0.6μmol/ mL的浓度范围内，所有化合物均未对RBC的完整性产生任何影响。

总之，就血浆止血而言，二甲双胍的磺酰胺衍生物具有潜在的有益特性，而血浆止血通常在T2DM患者中受损。因此，二甲双胍磺酰胺可能成为进一步设计和合成具有改善的药代动力学性质的新型二甲双胍类似物和前药的原型。