Mikov Momir, Al-Salami Hani, Golocorbin-Kon Svetlana, Skrbic Ranko, Raskovic Aleksandar, Fawcett J Paul
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Eur J Drug Metab Pharmacokinet. 2008 Jul-Sep;33(3):137-42. doi: 10.1007/BF03191110.
The aim of this study was to investigate the pharmacokinetics and glucose-lowering activity of gliclazide alone and in combination with the bile acid salt, sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC), in a rat model of type I diabetes. Eighty male Wistar rats were divided into eight groups (n=10). Four groups were treated with alloxan (30 mg/kg) to induce diabetes. One group of healthy and one group of diabetic rats were administered gliclazide (20 mg/kg), MKC (4 mg/kg) or a combination of gliclazide (20 mg/kg) and MKC (4 mg/kg). One group of healthy and one group of diabetic rats were used as controls. Blood samples were collected from the tail vein 6 hours post-dose and the plasma was analyzed for glucose concentrations. It was found that gliclazide bioavailability was increased in healthy rats when coadministered with MKC, but there was no difference in glucose levels. Gliclazide bioavailability was much lower in diabetic rats and was not altered by MKC. However, the hypoglycemic effect of the combination of gliclazide and MKC was significantly greater in diabetic rats than that of gliclazide alone. It was demonstrated that the combination of MKC and gliclazide produced a significant hypoglycemic effect in a rat model of Type I diabetes. As gliclazide alone does not have a hypoglycemic effect on Type I diabetic rats, it can be concluded that gliclazide potentiates hypoglycemic effect of MKC in Type I diabetic rats.
本研究旨在探讨在I型糖尿病大鼠模型中，格列齐特单独使用以及与胆酸盐3α,7α - 二羟基 - 12 - 酮 - 5β - 胆烷酸钠（MKC）联合使用时的药代动力学及降糖活性。80只雄性Wistar大鼠被分为8组（n = 10）。4组用四氧嘧啶（30 mg/kg）处理以诱导糖尿病。一组健康大鼠和一组糖尿病大鼠分别给予格列齐特（20 mg/kg）、MKC（4 mg/kg）或格列齐特（20 mg/kg）与MKC（4 mg/kg）的组合。一组健康大鼠和一组糖尿病大鼠作为对照。给药后6小时从尾静脉采集血样，分析血浆中的葡萄糖浓度。结果发现，在健康大鼠中，与MKC共同给药时格列齐特的生物利用度增加，但血糖水平无差异。在糖尿病大鼠中，格列齐特的生物利用度低得多，且不受MKC影响。然而，格列齐特与MKC联合使用对糖尿病大鼠的降糖作用明显大于单独使用格列齐特。结果表明，在I型糖尿病大鼠模型中，MKC与格列齐特联合使用产生了显著的降糖作用。由于单独使用格列齐特对I型糖尿病大鼠没有降糖作用，因此可以得出结论，格列齐特增强了MKC对I型糖尿病大鼠的降糖作用。
