Stetinová V, Kvetina J, Pastera J, Polásková A, Prazáková M
Institute of Experimental Biopharmaceutics, Joint Research Centre of the Czech Academy of Sciences and PRO.MED.CS Praha a.s., Hradec Králové, Czech Republic.
Biopharm Drug Dispos. 2007 Jul;28(5):241-8. doi: 10.1002/bdd.550.
The relationship between the pharmacokinetics of gliclazide and its antidiabetic efficacy were evaluated on the basis of experimental determination of changes with time in the plasma levels of this antidiabetic agent and those of glucose. The experiment included rats with both initial normal glycaemia and alloxan-induced hyperglycaemia (glycaemia increased by a minimum of 30%). Pharmacokinetic and pharmacodynamic parameters were examined in the interval of 30 to 180 min after p.o. administration of a single dose of 25 mg/kg of gliclazide. The drug was administered on day 4, following a single i.v. dose of either 50 mg/kg of alloxan (hyperglycaemic group) or the injection vehicle (control group). Even though the biological availability of gliclazide was similar in both normoglycaemic and hyperglycaemic animals, the gliclazide-induced hypoglycaemizing response was not uniform: until 60 min, the decrease of glycaemia was smaller in animals with alloxan hyperglycaemia (23% decrease at 60 min) in contrast to the normoglycaemic animals (36% decrease at 60 min), at later times, the intensity of this hypoglycaemizing effect of gliclazide persisted in the hyperglycaemic animals, while in the normoglycaemic ones, a reversal of the hypoglycaemizing effect occurred.
根据对该抗糖尿病药物及其血糖水平随时间变化的实验测定，评估了格列齐特的药代动力学与其抗糖尿病疗效之间的关系。实验包括初始血糖正常和四氧嘧啶诱导的高血糖（血糖至少升高30%）的大鼠。在口服单剂量25mg/kg格列齐特后30至180分钟的时间间隔内，检查药代动力学和药效学参数。在第4天给药，此前静脉注射单剂量50mg/kg四氧嘧啶（高血糖组）或注射溶媒（对照组）。尽管格列齐特在血糖正常和高血糖动物中的生物利用度相似，但格列齐特诱导的降血糖反应并不一致：直到60分钟，四氧嘧啶高血糖动物的血糖降低幅度较小（60分钟时降低23%），而血糖正常动物的血糖降低幅度较大（60分钟时降低36%），在随后的时间里，格列齐特的这种降血糖作用强度在高血糖动物中持续存在，而在血糖正常动物中，降血糖作用出现了逆转。
