摘要
目的研究红霉素在健康和糖尿病家兔体内对格列齐特片代谢的影响。方法健康新西兰家兔和实验性糖尿病家兔各8只,每只口服格列齐特80 mg,经2 wk清洗期后,每只家兔腹腔注射乳糖酸红霉素11.6 mL·kg^(-1),连续3 d,d 4口服相同剂量的格列齐特。所有家兔均在给予格列齐特后0.5、1.5、3、5、6、7.5、9、10.5、12、24、36 h经耳缘静脉采血,用HPLC法测定各点格列齐特的血浓度,血药浓度结果用3P97软件进行曲线拟合,采用自身对照法分析给予红霉素前后格列齐特药动学的变化。结果格列齐特在家兔体内的药动学符合单室模型,正常组家兔单用格列齐特,其t_(1/2ke)、ρ_(max)、AUC分别为(3.32±0.79)h、(39.48±6.63)mg·L^(-1)、(224.03±48.17)mg·h·L^(-1);加用红霉素后其t_(1/2ke)、ρ_(max)、AUC分别为(4.09±1.87)h、(48.79±15.5)mg·L^(-1)、(274.17±44.78)mg·h·L^(-1)。糖尿病组家兔单用格列齐特,其t_(1/2ke)、ρ_(max)、AUC分别为(3.35±0.67)h、(37.13±7.21)mg·L^(-1)、(233.51±39.60)mg·h·L^(-1);加用红霉素后其t_(1/2ke)、ρ_(max)、AUC分别为(4.18±1.79)h、(48.25±9.82)mg·L^(-1)、(295.63±44.78)mg·h·L^(-1)。给予红霉素前后格列齐特的t_(1/2ke)、ρ_(max)及AUC差异均存有统计学意义(P<0.05)。结论红霉素对家兔体内格列齐特的药动学有明显的影响。
AIM To study the influence of erythromycin on the pharmacokinetics of gliclazide （GL） in healthy and diabetic rabbits. METHODS GL （80 rag） was taken orally once to every rabbit. After 2 wk of cleaning stage, erythromycin （ 11.6 mg· kg^- 1 ） was administered daily by intra peritoneal injection for 3 d, then GL was taken orally at the same dosage on the d 4. The blood was drawn from ear vein at 0.5, 1.5,3,5,6,7.5,9, 0.5,12,24 and 36 h after administering GL in every rabbit. Then the blood concentration of GL was measured by HPLC. The pharmacokinetic parameter was calculated with 3P97 software. The pharmacokinetics of GL in rabbits administered with or without erythromycin were analyzed by auto-control. RESULTS The concentration-time curves were fit to the one-comparnent model. In healthy rabbits administered with GL, the t1/2ke,ρmax, AUC values were（3.32 ± 0.79）h, （39.48 ± 6.63）mg·L^-1 and （224.03 ± 48.17） mg· h· L^- 1. In healthy rabbits administered with GL and erythromycin, the t1/2ke, ρmax, AUC values were（4.09 ±1. 87）h, （48.79 ± 15.5）mg·L^1 and （274.17 ± 44.78）mg·h· L^-1. In diabetic rabbits administered with GL, the t1/2ke,ρmax,AUC values were （3.35 ± 0.67）h, （37.13 ± 7.21）mg·L^-1, （233.51 ± 39.60）mg·h·L^-1. In diabetic rabbits administered with GL and erythromycin, the t1/2ke, Pmax, AUC values were （4.18 ± 1.79） h, （48.25 ± 9.82） mg-L- 1, （295.63 ± 44.78）mg· h· L^- 1. There were notable differences on t 1/2ke, ρmax, AUC values of GL in rabbits administered with or without erythromycin. CONCLUSION Erythromycin shows significant inhibition on the pharmacokinetics of GL.
出处
《中国临床药学杂志》
CAS
2007年第5期293-296,共4页
Chinese Journal of Clinical Pharmacy
基金
台州市科委课题(NO.011227)
浙江省药剂学专业委员会医院药学基金资助(编号:010105)。
关键词
红霉素
格列齐特
相互作用
糖尿病
家兔
erythromycin
gliclazide
interaction
diabetes mellitas
rabbit
