Kim Hosoon, Yun Minhyuk, Kwon Kwang-il
College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea.
Arch Pharm Res. 2003 Jul;26(7):564-8. doi: 10.1007/BF02976882.
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.
在健康志愿者口服格列齐特片后，对其药代动力学和药效学特性进行了研究。经过一夜禁食后，给11名志愿者口服格列齐特片。另外10名志愿者作为对照组（即未服用格列齐特）。采集血样，测定给药后24小时内格列齐特和葡萄糖的浓度。对格列齐特进行了标准药代动力学分析。药物的药效学活性通过葡萄糖浓度的增加（deltaPG）、葡萄糖浓度-时间曲线增加部分的面积（AUC(deltaPG)）或给药组和未给药组在各时间点葡萄糖浓度增加的差异（D(deltaPG)）来表示。药代动力学分析显示，格列齐特的Cmax、Tmax、CL/F（表观清除率）、V/F（表观分布容积）和半衰期分别为4.69±1.38mg/L、3.45±1.11小时、1.26±0.35L/h、17.78±5.27L和9.99±2.15小时。与未给药组相比，格列齐特在1、1.5、2、2.5、3和4小时时显著降低了AUC(deltaPG)（p<0.05）。deltaPG在1和1.5小时时与AUC(格列齐特)呈正相关（p<0.05），给药后1小时时相关系数最大（r = 0.642），4小时时逐渐降低。AUC(deltaPG)在1、2、3和4小时时与AUC(格列齐特)呈正相关（p<0.0
