摘要
目的建立加替沙星的反相高效液相色谱分析方法,并对其肝损害模型动物体内过程与药代动力学进行分析研究。方法健康和肝损害造模大鼠口服加替沙星后测定各组织药物浓度,收集尿液、胆汁与粪便,测定累积排泄率;测定各时间点肝损害家犬中加替沙星浓度,计算其药动学参数。结果健康和肝损害造模大鼠口服20 mg.kg-1加替沙星后,快速分布在各组织中,其中肝、肾、小肠、胃分布最多,大脑未测到药物。口服20 mg.kg-1加替沙星后48h,尿液、胆汁与粪便药物累及排泄率分别为(66.2±8.8)%与(71.2±13.6)%(、8.1±3.1)%与(1.6±0.7)%和(3.6±1.7)%与(3.9±1.9)%。加替沙星在健康家犬与肝损家犬体内呈一室模型,主要药动学参数tmax为(2.4+0.8)h和(1.1+0.3)h,Cmax为(2.3+0.1)mg.L-1和(2.6+0.1)mg.L-1,AUC为(33.8+6.8)!g.h.ml-1和(36.8+4.7)!g.h.ml-1。结论加替沙星在肝损害模型大鼠组织分布和尿液、粪便的排泄未受到影响,胆汁排泄存在统计学差异,体内药动学参数经统计学分析,不存在显著性差异(P>0.05),说明肝脏损害对加替沙星的药动学无显著性影响。通过了解加替沙星体内过程,可为临床应用提供参考。
Objective To establish HPLC method for determination of gatifloxacin and to,analyze in vivo course and pharmacokinetics in animals model of liver damaged. Methods After a single of 20mg·kg^-1 gatifloxacin administered in animels model of to normal and liver damaged rats, tissues of drug concentrations were determined,and the urinary, bile and dejection accumulative excretions were also determined. Use the assay HPLC method to examine the concentration of Gatifloxacin in liver damaged dogs and calculate the pharmacokinetic parameters. Results After administered a single of 20mg·kg^-1 gatifloxacin to normal and liver damaged rats, the drug concentrations was rapidly and extensively distributed to all tissues, especially in liver, intestines, stomach and kidney. Gatifloxacin were not determined in brains. The urinary, bile and dejection accumulative excretions in rats were （66.2±8.8）% and （71.2±13.6）%, （8.1±3.1）% and （1.6±0.5r）%, （3.6± 1.7）% and （3.9±1.9）% respectively. The pharmacokinetic process of normal and liver damaged dogs fitted to one compartment model. The main pharmacokinetic parameters of gatifloxacin were as follow were tmax （2.4±0.8）h and （1.1±0.3）h,Cmax were （2.3±0.1） mg·L^-1 and （2.6±0.1） mg·L^-1, AUC0-24 were（33.8±6.8）μg·h·ml^-1 and（36.8±4.7）μg·h·ml^-1 Conclusions Gatifloxacin was influenced in tissues distribution and urinary and dejection to liverdamaged rats. The bile excreted of gatifloxacin showed significant difference. The main pharmacokinetic parameters of gatifloxacin in liver damage dogs and normal dogs have not to show the difference. Understanding in vivo course of gatifloxacin will offer the reference for the clinical application.
出处
《药品评价》
CAS
2006年第5期358-361,共4页
Drug Evaluation
基金
广西自然科学基金资助(编号:0249016)
关键词
加替沙星
药代动力学
组织分布
肝损害
动物
Gatifloxacin
pharmacokinetics
tissues distribution
liver damage
animal
