泛昔洛韦缓释微丸体内测定方法的建立及药动学研究

目的：建立泛昔洛韦（FCV）缓释微丸体内血药浓度的测定方法并进行体内药动学研究。方法：以甲醇和0.02mol/L磷酸二氢钾（9∶91）为流动相,选择6条家犬口服泛昔洛韦缓释微丸375mg后,利用高效液相色谱法（HPLC）测定6条家犬的血药浓度并对其进行药动学的研究。结果：本法的线性范围为0.1-10μg/ml,r=0.9943,日内及日间RSD均小于10%。FCV缓释微丸在体内的代谢产物喷昔洛韦（PCV）的tmax为（4.80±0.84）h,Cmax为（2.61±1.37）mg/L,AUC0→∞为（25.59±7.58）mg/h/L,MRT为（9.85±2.47）h。结论：本方法简便快速,无干扰,重现性好,可用于泛昔洛韦在体内的药动学研究,并且通过本实验的体内测定方法得到了家犬体内的药动学参数。

Studies on Determination of Plasma Concentration and Pharmacokinetics of Famciclovir Sustained Release Pellets in Dogs

Objective： To establish a HPLC method for determining plasma PCV concentration and study the pharmacokinetics of FCV sustained release pellets in dogs. Method： Methanol- 0.02mol/L KH2PO4 （9：91 ） was used as mobile phase, a single dose of 375 mg of FCV sustained release pellets were given to 6 dogs. The drug concentrations in plasma were determined by HPLC method and the pharmacokinetic parameters were measured. Result： PCV plasma concentration had a good linear relationship from 0. 1 μg/mL to 10.0μg/mL, （ r =0.9990） , RSD of intra - day and inter - day were less than 10%, respectively. The average recovery rate was 97.18%. The pharmacokinetic parameters of the metabolic product penciclovir （ PCV ） of FCV sustained release pellets were tmax （ 4.80 ± 0.84 ） h, Cmax （ 2.61 ± 1.37 ）mg/L, AUC0→∞ （ 26. 35 ± 1.69 ） mg/h/L, MRT （ 10.13 ± 2.24 ） h, respectively. Conclusion： The method was rapid, simple, reproducible, and impurities in plasma did not interfere. It could be used for the studies on pharmacokinetics of FCV sustained release pellets. The pharmacokinetic parameters in dogs were got by this method.