Beagle犬血浆中头孢克洛浓度的测定及其不同工艺制备的干混悬剂药动学比较  

Determination of cefaclor in beagle dog plasma and pharmacokinetics comparison of cefaclor for suspensions prepared by different techniques

作　　者：唐宽锦 吕怡沁 张天虹[1] TANG Kuanjin;LYU Yiqin;ZHANG Tianhong(Wuya Collage of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学无涯创新学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2023年第7期890-898,共9页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立测定Beagle犬血浆中头孢克洛质量浓度的分析方法,以比较不同工艺制备的头孢克洛干混悬剂的药动学行为。方法采用双周期交叉试验设计,将采用流化床一步制粒和湿法制粒制备的头孢克洛干混悬剂分别口服给予6只健康Beagle犬,应用所建立的分析方法测定Beagle犬血浆中头孢克洛的浓度,并计算主要药动学参数。结果血浆中头孢克洛在0.1558~49.87 mg·L^(-1)质量浓度范围内线性关系良好(r=0.9998),定量下限为0.1558 mg·L^(-1),日内、日间精密度在2.6~13%内,准确度RE在-1.6%~-5.6%内。采用流化床一步制粒和湿法制粒制备的头孢克洛干混悬剂处方组成相同,但颗粒形态和药物在颗粒中分布位置不同,二者主要药动学参数:ρmax分别为17.34和16.80 mg·L^(-1);tmax分别为1.92和2.00 h;AUC0-t分别为64.66和62.15 mg·h·L^(-1)。结论该方法满足生物样品的测定要求,可用于Beagle犬血浆中头孢克洛质量浓度的测定,采用不同工艺制备的头孢克洛干混悬剂主要药动学参数无统计学差异。Objective To establish an analytical method for the determination of cefaclor in beagle dog plasma and apply the method to compare the pharmacokinetics of cefaclor for suspensions prepared by different techniques.Methods The in vivo pharmacokinetic study performed in a randomized,open-label,2×2 crossover trial.Cefaclor for suspensions prepared by fluidized bed one-step granulation and wet granulation were administered to 6 healthy beagle dogs.Plasma concentration of cefaclor was determined by established method and the main pharmacokinetics parameters were calculated.Results The linear range was 0.1558-49.87 mg·L^(-1) and the lower limit of quantitation was 0.1558 mg·L^(-1).The intra-day and interday precision ranged from 2.6%to 13%and the accuracy ranged from-1.6%to-5.6%.Although cefaclor for suspensions were prepared by fluidized bed one-step granulation and wet granulation with the same prescription,the particle morphology and drug distribution position in the particles were different.The main pharmacokinetics parameters of cefaclor for suspensions were as follows:ρmax(mg·L^(-1)):17.34 and 16.80;tmax(h):1.92 and 2.00;AUC0-t(mg·h·L^(-1)):64.66 and 62.15.Conclusion The analytical method meet the requirements of biological sample determination,which can be applied to determination of cefaclor in beagle dog plasma.There is no statistical difference in the main pharmacokinetics parameters of cefaclor for suspensions prepared by different techniques.

关 键 词：头孢克洛 干混悬剂 制备工艺 药动学 

分 类 号：R917[医药卫生—药物分析学]