吡喹酮单独和联合狂犬弱毒疫苗对家兔给药后血浆药物动力学研究

Pharmacokinetics of Praziquantel after Single and Combined with Attenuated Rabies Vaccine in Rabbit Plasma

关键词:  吡喹酮  狂犬病弱毒苗-吡喹酮复合制剂  HPLC  血药浓度  药代动力学

Key words:  praziquantel  combined with Attenuated rabies vaccine  HPLC  concentration-time relationship  Pharmacokinetics

摘要:

为测定单独给药及联合狂犬弱毒疫苗制剂给药后家兔血浆的血药浓度，建立了以乙腈/水为流动相进行梯度洗脱的HPLC方法测定血浆中吡喹酮的含量，并初步研究其药代动力学特点。实验组分为对照组(生理盐水)、7%吡喹酮注射剂组与狂犬疫苗-吡喹酮复合制剂组,空腹12 h后肌注,在给药后不同时间点耳廓静脉采血,处理血样后HPLC测定。采用DSA软件处理血药浓度数据的药代动力学参数。吡喹酮峰保留时间在15.10 min、无杂峰干扰，且拖尾因子和塔板数均符合要求，HPLC方法学验证表明吡喹酮的标准曲线在2～16 μg/mL范围内线性良好(R2=0.9996)，其稳定性、重复性及加样回收率均符合生物样品测定要求。狂犬弱毒疫苗-吡喹酮复合制剂给药后，血浆中吡喹酮含量的变化趋势与吡喹酮单独给药呈现相似的代谢规律，即15 min后迅速增加，在1 h达到峰值，4 h含量达到低值，此后代谢缓慢，在24 h仅能检测到微量吡喹酮。通过研究单独和联合狂犬弱毒疫苗制剂给药后家兔血浆中吡喹酮的药代动力学过程，初步阐明了其体内药物吸收和代谢过程，为临床安全合理给药提供参考。

Abstract:

Pharmacokinetics of praziquantel after intramuscular injection of single and combined with attenuated rabies vaccine to rabbit were studied. HPLC method was estabilshed for the determination of praziquantel in rabbit plasma with gradient elution using the acetonitrile-water flow. Rabbits were divided into the control group (normal saline)， 7% praziquantel group and praziquantel combined with attenuated rabies vaccine group, three groups were injected in muscle after 12 hours of fasting, blood samples were collected by vein at different time after the administration, and praziquantel concentrations in the blood samples were determined by established HPLC method.The retention time of praziquantel appeared at 15.10 min and no interference of peaks, and the tailing factor and the number of plates meet the requirements. HPLC method validation showed that the standard curve of praziquantel is 2～16 μg/mL, R2=0.9996. The precision, stability and sample recovery meet the biological sample measurement requirements. The concentration-time curves of praziquantel were similar between single and combined with attenuated rabies vaccine injection. The concentration was increased rapidly after 15 min, peaked at 1 h, and reached a low value at 4 hours. After that, the metabolism turned slowly, and there was no praziquantel detected after 24 h. In this study, the pharmacokinetic of praziquantel in rabbit plasma after single administration and combination of rabies attenuated vaccine provided preliminary research on drug absorption and metabolic processes in vivo,which provides reference for clinical safe and reasonable administration.