奥拉西坦在犬体内的药动学研究

Study on Pharmacokinetics of Oxiracetam in Dogs

目的：研究奥拉西坦在Beagle犬体内的药动学特性。方法：取5只Beagle犬单剂量灌胃奥拉西坦100 mg/kg,以吡拉西坦为内标,采用高效液相色谱法测定给药前及给药后0.25、0.5、0.75、1、1.5、2、3、4、6、8、12、24 h血浆中奥拉西坦的浓度,DAS 2.0软件计算药动学参数。色谱条件采用色谱柱为Luna C18,流动相为乙腈-水（含5 mmol/L醋酸铵,0.1%醋酸）（80∶20）,流速为1.0 ml/min,检测波长为210 nm,进样量为20μl,柱温为40℃。结果：奥拉西坦检测质量浓度的线性范围为2.0~160.0μg/m（lr=0.998 2）,平均方法回收率为93.5%~101.3%,日内和日间RSD均〈15%（n=5）;奥拉西坦在犬体内的吸收符合一室模型,药动学参数分别为cmax（94.20±20.12）μg/ml、V/F（38.72±20.3）L、tmax（1.79±0.51）h、t1/2（3.08±0.73）h、AUC0-24 h（285.02±52.41）μg·h/ml。结论：本方法可用于奥拉西坦的血药浓度测定;奥拉西坦在犬体内的吸收较快,消除迅速。

OBJECTIVE： To study pharmacokinetics characteristics of oxiracetam in Beagle dogs. METHODS： 5 Beagle dogs were given oxiracetam 100 mg/kg intragstrically. Using piracetam as internal standard, the concentrations of oxiracetam were deter- mined by HPLC before medication and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h after medication. Pharmacokinetic pa- rameters were calculated using DAS 2.0 software. The determination was performed on Luna C18 column with mobile phase consist- ed of acetonitrile-water （5 mmol/L ammonium acetate, 0.1% acetic acid）（80：20） at the flow rate of 1.0 ml/min. The detection wavelength was set at 210 nm and column temperature was 40℃. The sample size was 20 μl. RESULTS： The linear range of oxi- racetam was 2.0-160.0 μg/ml （r= 0.998 2）. Average recovery rates were 93.5%-10t.3 %. RSDs of inter-day and intra-day were less than 15% （n=5）. The pharmacokinetics of oxiracetam in Beagle dogs conformed with one-compartment model. The main pharma- cokinetic parameters of oxiracetam were as follows： Cmax（94.20 ± 20.12） μg/ml, V/F（38.72 ± 20.3） L, Imp, （1.79 ± 0.51） h, t1/2 （3.08 ± 0.73） h, AUC0-24h （285.02 ± 52.41） μg.h/ml. CONCLUSIONS： The method is suitable for the determination of plasma con- centration of oxiracetam. Oxiracetam is absorbed and eliminated rapidly in dog.