内向整流钾通道6.2基因E23K多态性与2型糖尿病表型及格列齐特降糖疗效的关系

研究内向整流钾通道6．2（Kir6．2）基因E23K多态性对2型糖尿病临床表型及格列齐特降糖疗效的影响。结果提示K／K纯合子患者的血肌酐水平高于其它基因型患者（P〈0．01），E23K多态性不影响格列齐特的降糖疗效。     

Effect of gliclazide modified release on adiponectin,interleukin‐6, and tumor necrosis factor‐α plasma levels in individuals with type 2 diabetes mellitus

ABSTRACT

Objective: The aim of the study was to evaluate the effect of gliclazide modified release (MR) treatment on adiponectin, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF‐α) plasma concentrations in type 2 diabetic patients.

Research design and methods: 24 randomly selected type 2 diabetic patients, aged 61.2 ± 15.4 years, with poorly controlled glucose level (mean glycated hemoglobin [HbA_1c] 7.6 ± 1.1%) despite treatment with diet and/or oral hypoglycemic agents, were included in the study. All of the patients, after a 2‐week run-in period, were given gliclazide MR for 12 weeks. At baseline, and after gliclazide MR treatment, HbA_1c and plasma concentrations of IL‐6, TNF‐α, and adiponectin were measured.

Results: Gliclazide MR treatment produced significant reductions in fasting plasma glucose (from 7.6 ± 1.4 to 6.6 ± 1.2?mmol/L, p < 0.01), HbA_1c (from 7.6 ± 1.1 to 6.9 ± 0.8%, p < 0.01), and plasma IL‐6 concentrations (from 2.5 ± 1.8 to 1.8 ± 1.2?pg/mL, p < 0.05). A significant increase in plasma adiponectin level was noted (from 6.4 ± 3.3 to 7.6 ± 4.4?µg/mL, p < 0.05). Plasma TNF‐α concentrations and homeostasis model assessment of insulin resistance (HOMA‐IR) decreased after treatment, but these changes did not reach statistical significance.

Conclusions: Gliclazide MR improves glycemic control and, in addition, has a positive influence on the plasma level of some inflammatory markers and adiponectin. Increased plasma adiponectin and decreased plasma IL‐6, and TNF‐α levels may explain, at least in part, the anti-atherogenic action of this drug reported elsewhere.     

格列喹酮对胰岛β细胞株HIT—T15细胞的促胰岛素分泌作用

目的通过观察不同葡萄糖浓度下格列喹酮（Glq）刺激HIT-T15细胞分泌胰岛素的作用,了解Glq对β细胞的刺激模式。方法HIT-T15细胞孵育于5、10、15mmol／L葡萄糖浓度的培养基中,8小时后加入Glq、格列本脲（Glb）、格列齐特（GIc）,分别在不同时间点收集培养液,测定药物刺激前后的胰岛素分泌水平。结果在三种糖浓度下,Glq刺激的胰岛素分泌高峰均在加药后10分钟,在30分钟时又有一稍低的第二峰,随后逐渐下降,至180分钟后分泌速率为基础值的1．1～1．2倍;Glb呈单相分泌峰,峰值出现在45分钟,随后分泌速率逐渐下降,至180分钟后仍有基础值的1．5倍;在10 mmol／L糖浓度组,Glq刺激的胰岛素浓度时间曲线下面积（AUC）更小。Glc的分泌曲线类似Glq。结论Glq与Glb对β细胞的刺激作用模式不同,前者较后者胰岛素分泌达峰时问更快、作用时间更短,AUC更小。     

复方丹参滴丸辅助治疗2型糖尿病观察60例

目的研究复方丹参滴丸辅助治疗2型糖尿病的临床效果。方法选择120例2型糖尿病患者,随机平分为对照组和治疗组各60例,对照组服用格列齐特缓释片、阿卡波糖片;治疗组在对照组用西药格列齐特缓释片、阿卡糖片的基础上加服复方丹参滴丸,疗程10周。结果对照组有效率56．7％,治疗组有效率81．7％,两组总有效率比较有显著差异（χ^2=5．68,P〈0．05）。治疗组与对照组治疗10周后,空腹血糖（FBG）,餐后2h血糖（P2BG）,糖化血红蛋白（HbAle）,血胆固醇（TC）及三酰甘油（TG）均显著下降,且治疗组上述指标改善更明显。结论复方丹参滴丸辅助治疗2型糖尿病的疗效良好,值得临床推广。     

格列齐特普通片改为格列齐特缓释片治疗2型糠尿病的临床观察

目的：评价服用格列齐特缓释剂（格列齐特释片30mg片剂）治疗12周后,对2型糖尿病患者总体控制的有效性,并与普通剂型比较。方法：100例2型糖尿病患者随机分为两组治疗,一组为开始使用单纯格列齐特普通制剂,在观察开始时改为使用格列齐特缓释剂组,一组为普通剂型格列齐特组。治疗12周后以其两组的糖基化血红蛋白（HbA1c）,空腹血浆葡萄糖各自的对比,评价服用格列齐特缓释片对2型糖尿病的有效性及对比普通制剂的优越性。同时通过对副作用．特别是低血糖的出现情况的统计,评价12周治疗对2型糖尿病病人的安全性与普通制剂的对比。结果：12周治疗后,100例患者使用格列齐特缓释剂后和之前使用普通剂型对比的血糖化血红蛋白水平非常接近,组间差异无统计学意义,表明临床疗效相当。两组血糖日均值也相近。两组经血糖监测观察到低血糖发作次数差异无统计学意义。患者依从性的对比,格列齐特缓释片优于达美康普通片,并且无病人因不良事件出观察。观察中无严重不良事件发生。结论：格列齐特缓释剂与普通剂的疗效相似且安全性更佳。     

近红外光谱对血浆中格列齐特浓度的检测

目的建立一种高效无损检测格列齐特血药浓度的方法 .方法采用近红外光谱法检测,近红外光谱的检测范围为12500~4000cm-1,分辨率4cm-1,扫描次数为64次.结果偏最小二乘回归在6200~5400cm-1范围内进行分析,检测浓度范围在0.05~2.15μg·mL-1,RMSECV和RMSEP分别为0.153和0.467.结论用近红外光谱对格列齐特血药浓度的测定是可行的.     

Spectrophotometric determination of gliclazide in pharmaceuticals and biological fluids through ternary complex formation with eosin and palladium (II)

A simple and sensitive spectrophotometric method has been developed for the determination of gliclazide (GLZ) in pharmaceutical formulations and biological fluids. The proposed method is based upon the formation of a ternary complex between palladium (II), eosin and GLZ in the presence of methyl cellulose as a surfactant and acetate buffer of pH 4.5. The ternary complex showed an absorption maximum at 550 nm. The solution of ternary complex obeyed Beer's law over the concentration range of 0.5-4 microg ml(-1) with minimum detectability (S/N = 2) of 0.05 microg ml(-1) (1.545 x 10(-7) M). The different experimental parameters affecting the development and stability of the color were carefully studied and optimized. The proposed method was successfully applied to the analysis of commercial tablets. The results obtained were in good agreement with those obtained using the official or reference spectrophotometric method. The proposed method was further applied to spiked human urine and plasma, the percentage recoveries were 97.84 +/- 0.72 and 97.43 +/- 0.83, respectively, (n = 4). A proposal of the reaction pathway was presented.     

Pharmacokinetic and pharmacodynamic characterization of gliclazide in healthy volunteers

Pharmacokinetic and pharmacodynamic properties of gliclazide were studied after an oral administration of gliclazide tablets in healthy volunteers. After an overnight fasting, gliclazide tablet was orally administered to 11 volunteers. Additional 10 volunteers were used as a control group (i.e., no gliclazide administration). Blood samples were collected, and the concentration determined for gliclazide and glucose up to 24 after the administration. Standard pharmacokinetic analysis was carried out for gliclazide. Pharmacodynamic activity of the drug was expressed by increase of glucose concentration (deltaPG), by area under the increase of glucose concentration-time curve (AUC(deltaPG)) or by the difference in increase of glucose concentration (D(deltaPG)) at each time between groups with and without gliclazide administration. Pharmacokinetic analysis revealed that Cmax, Tmax, CL/F (apparent clearance), V/F (apparent volume of distribution) and half-life of gliclazide were 4.69+/-1.38 mg/L, 3.45+/-1.11 h, 1.26+/-0.35 L/h, 17.78+/-5.27 L, and 9.99+/-2.15 h, respectively. When compared with the no drug administration group, gliclazide decreased significantly the AUC(deltaPG) s at 1, 1.5, 2, 2.5, 3 and 4 h (p<0.05). The deltaPGs were positively correlated with AUC(gliclazide) at 1 and 1.5 h (p<0.05), and the correlation coefficient was maximum at 1 h (r = 0.642) and gradually decreased at 4 h after the administration. The AUC(deltaPG)s were positively correlated with AUC(gliclazide) at 1, 2, 3 and 4 h (p<0.05), and the maximum correlation coefficient was obtained at 2 h (r=0.642) after the administration. The D(deltaPG) reached the maximum at 1 h, remained constant from 1 h to 3 h, and decreased afterwards. Therefore, these observations indicated that maximum hypoglycemic effect of gliclazide was reached at approximately at 1.5 h after the administration and the effect decreased, probably because of the homeostasis mechanism, in health volunteers.     

Effect of insulin and gliclazide on glucose utilization by a perfused intestine-pancreas preparation isolated from diabetic and non-diabetic rats

The effect of insulin (40 U/ml) and gliclazide (200 g/ml) on intestinal glucose metabolism was investigated by using an in vitro perfuse intestine-pancreas preparation isolated from normal or streptozotocin-diabetic rats. Glucose, lactate and alanine were measured enzymatically in the portal effluent. The glucose retained by the perfused preparation was reduced (P<0.05) in diabetic versus control rats. The portal lactate levels were not modified, but alanine portal levels were increased (P<0.05) in diabetic versus control rats. In the diabetic rats, the level of glucose retained by the preparations was increased (P<0.05) by the presence of insulin, and insulin plus gliclazide in the perfusate. In the presence of insulin and/or gliclazide, the portal lactate levels were not modified, but the alanine levels were reduced (P<0.05) to normal values. In preparations from non-diabetic rats, the level of glucose retained was increased (P<0.05) by gliclazide and insulin plus gliclazide, without modification of the portal lactate and alanine levels. In conclusion, the results show that both insulin and gliclazide increased glucose utilization by perfused intestine-pancreas preparations isolated from diabetic rats. The effect was enhanced when both substances were present simultaneously in the perfusion medium.Presented in part at the 26th annual meeting of the European Association for the Study of Diabetes, Copenhagen, 10–13 September 1990, and at the 4th meeting of the Mediterranean Group for the Study of Diabetes, Madrid, 4–7 March 1993     

不同厂家格列齐特片溶出度考察

目的 :比较6厂家格列齐特片的溶出度 ,为临床选用提供参考。方法 :采用分光光度法分别测定A、B、C、D、E、F厂格列齐特片的累积溶出度 ,绘制其溶出曲线 ,计算参数T50、Td、m的值 ,并对T50、Td 值进行两两比较。结果 :E厂格列齐特片的T50、Td 值与其它5厂有显著性差异 (P<0 01) ,其余5厂格列齐特片的T50、Td 值间无显著性差异 (P>0 05)。其中 ,E厂格列齐特片在180min时的累积溶出率<75 %,不符合《中国药典》规定 ,其它5厂格列齐特片的溶出度均符合规定。结论 :建议有关厂家对影响制剂溶出度的辅料及生产工艺进行改进 ,以提高产品质量。