硫酸头孢噻利在兔体内的药动学研究

目的:研究硫酸头孢噻利在兔体内的药动学。方法:取兔15只,随机分为低、中、高剂量(硫酸头孢噻利75、150、300mg·kg-1)组,耳缘静脉注射给药,给药前分别采集血样和尿样,再于给药后5、10、15、30、45、60、80、100、120、150、180、240、360min采集血样,给药后0～2、2～4、4～6、6～8、8～12h收集尿样,采用高效液相色谱法测定不同时间点血样和尿样中头孢噻利的浓度,并计算药动学参数。结果:头孢噻利在兔体内药动学呈一房室模型,主要药动学参数t1/2分别为(0.87±0.03)、(0.88±0.04)、(0.86±0.04)h;cmax分别为(210.54±28.92)、(362.66±47.86)、(805.46±61.11)mg·L-1;AUC(0～6h)分别为(288.52±38.79)、(495.12±64.78)、(1095.81±75.34)mg·h·L-1。12h时尿药累积排泄量已达坪值,累积排泄率约为68.44%～72.29%。结论:硫酸头孢噻利在75～300mg·kg-1范围内,在兔体内的药动学行为符合线性关系,呈一级动力学分布、消除过程。

Pharmacokinetics Study of Cefoselis Sulfate in Rabbits

OBJECTIVE：To study pharmacokinetics of cefoselis sulfate in rabbit.METHODS：15 rabbits were randomly divided into high-dose group（75 mg·kg -1 ）,medium-dose group（150 mg·kg -1 ）and low-dose group（300 mg·kg -1 ）.3 groups were given medicine via ear vein.Blood sample and urine sample were collected before administration.Then blood samples were collected at 5 min,10 min,15 min,30 min,45 min,60 min,80 min,100 min,120 min,150 min,180 min,240 min and 360 min after administration.The urine samples were collected at 0～2 h,2～4 h,4～6 h,6～8 h,8～12 h after administration.The concentrations of cefoselis in blood samples and urine samples were determined by HPLC.The pharmacokinetic parameters were calculated. RESULTS：Pharmacokinetics of cefoselis in rabbits conformed to one-compartment mode.Main pharmacokinetic parameters were as follows：t 1/2 ：（0.87±0.03）h,（0.88±0.04）h and（0.86±0.04）h;c max ：（210.54±28.92）mg·L -1 ,（362.66±47.86）mg·L -1 and （805.46±61.11）mg·L -1 ;AUC （0～6 h） ：（288.52±38.79）mg·h·L -1 ,（495.12±64.78）mg·h·L -1 and（1 095.81±75.34）mg·h·L -1 , respectively.The accumulative urinary excretion at 12 h was up to average value with accumulative excretion rate of 68.44%～ 72.29%.CONCLUSION：The pharmacokinetics of cefoselis sulfate（75～300 mg·kg -1 ）in rabbit conforms to linear relationship and first-order kinetics.