扑热息痛温度敏感凝胶家兔体内药动学研究

Pharmacokinetics of Paracetamol Thermosensitive Hydrogel experiment with Rabbits

目的考察扑热息痛温敏凝胶直肠给药后在家兔体内的血药浓度经时过程。方法12只家兔随机均分成4组，按30mg·kg-1经直肠给与扑热息痛温敏凝胶栓剂、S-40酯栓剂、普通栓剂、普通凝胶剂。并分别于给药后5、15、30、45、60、90、120、180、240、360、480min，耳缘静脉取血，采用高效液相色谱法检测血清中的药物浓度，计算药物动力学参数。结果扑热息痛温敏凝胶组零到无限大时间曲线下面积（area under the concentration time-curves from time zero to infinity, AUCO→∞）为（1203．5±132_3）μg·min·ml-1。显著高于普通栓剂组（875．9±73．1），（996．8±149．7）μg·min·ml-1（P=0．016），最大血药浓度（mlaxinlum concentration，Cmax）（13．5±2．6）mg·L-1；显著高于其他各组（舟0．0002）。各组间其他药代动力学参数未见显著性差异。结论与其他三种制剂相比，扑热息痛温敏凝胶直肠给药后，Cmax显著升高，AUC略有增加，表明该制剂经直肠给药后可达到更高的血药浓度，但生物利用度之间没有显著性差异。温敏凝胶有望成为一种简便而有效的扑热息痛直肠给药载体。

Objective To study the pharmacokinetics of paracetamol given in thermosensitive hydrogel, S-40 ester suppository, traditional suppository, and general gel respectively in rabbits after rectal administration. Methods Paraeetamol was made into Twelve rabbits were randomly divided into 4 equal groups and received the four preparations rectally.The four preparations were the thermosensitive hydrogel, the S-40 ester suppository, the traditional suppository and general gel, respectively. 5, 15, 30, 45, 60, 90, 120, 180, 240, 360, and 480 min rectal administration later venous blood samples were collected to undergo high-performance liquid chromatography to test the serum concentration of paraeetamol. And the Pharmacokinetic parameters of the four paracetamol preparations were eaculated.Results The area under the concentration time-curves from time zero to infinity （AUCO→∞）of the thermosensitive hydrogel group was （1203.5±132.3）μg·min· ml-1, significantly higher than that of the general gel group （875.9±73.1）μg·min· ml-1,, P=-0.016）, and the maximum concentration （Cmax） of the thermosensitive hydrogel group was （13.5 ±2.6）mg· L-l;, significantly higher than those of the other 3 groups （all P=0.0002）. And there were not significant differences in other pharmacokinetic parameters among these 4 groups. Conclusion Compared with the other three preparations, the Cmax thermosensitive hydrogel preparation of paracetamol is greatly increased; however, the extent of bioavailability is not significantly deferent. Thermosensitive hydrogel can be an effective and convenient delivery system of rectally given paracetamol.