纳曲酮植入剂不同动物体内的药物释放和吸收

 目的 考察纳曲酮植入剂体内外药物释放的相关性，并比较植入动物种类和部位对植入剂体内结果的影响。方法 以聚乳酸为控释基质制备纳曲酮植入剂，γ-射线照射灭菌后，手术植入小鼠、大鼠、白兔和狗等不同动物，用紫外分光光度法测定体内外药物释放，用HPLC测定血浆和组织药物浓度。结果 不同动物及部位植入后，纳曲酮植入剂的体内药物释放均与体外药物释放具有良好的相关性，动物品种对药物释放的影响比相同动物不同植入部位的影响略大；单次植入给药后，小鼠、大鼠、白兔的体内血药浓度以及小鼠和大鼠肝、肾组织中的药物浓度和药物总量在28 d内保持平稳。结论 纳曲酮植入剂的体内外药物释放相关性良好，单次植入给药可以维持疗效4周以上。

In vivo release and absorption of naltrexone implants in different species of animals

OBJECTIVE To investigate the effects of the differences of animal species and implant locations on absorption in vivo and the correlation of the release in vitro and the absorption in vivo.METHODS Naltrexone implants (NTXIMPs) were implanted subcutaneously in mice,rats,rabbits and dogs,respectively,and also implanted intramuscularly in rabbits.The in vivo liberation of NTX from implants was detected by measuring the residual NTX amount in the implants using spectrophotometrical method.The absorption of NTX was monitored through measurement of the NTX concentrations in plasma,liver and kidney using HPLC.RESULTS Although the differences of animal species and implant locations affected the in vivo release profiles of NTXIMPs,the correlation between in vivo and in vivo release of NTX from implants were excellent (P<0.01).The difference of in vivo release of NTX from implants was dependent on the adipose tissue distribution.The effects of the different animal species was a little more remarkable than that of different implant locations on in vivo release of NTX from implants.A fairly constant NTX plasma level was observed during the implantation in all the animal species studied,indicating that NTXIMPs could maintain fourweek therapeutic effects after subcutaneous implantation.The constant NTX concentrations and total amounts in the liver and kidney of mice and rats also indicated that there was no drug accumulation during implantation.CONCLUSION In vivo release profiles of NTXIMPs were affected by both the different animals species and different implant locations.Good correlation of in vitro and in vivo release was observed in NTXIMPs.Single implantation of NTXIMPs may maintain the therapeutical effect more than 4 weeks.