摘要
目的 评价一种可注射的纳曲酮微球缓释制剂在 4条犬体内的药物释放过程 ,生物相容性和生物降解性情况。方法 用高效液相色谱 电化学检测器法 ,以纳洛酮为内标来研究纳曲酮的药代动力学数据和注射局部残留微球中的纳曲酮含量 ,在肉眼和显微镜两个水平进行注射局部的组织病理学检查。结果 犬im 0 .5或 1 .0mg·kg-1盐酸纳曲酮的药代动力学研究得出其血浆清除率为 0 .66～ 0 .73L·min-1,t1/2 β为 60 .0～ 67.2min,经过 1周的无药物处理的清除期 ,进入 4周的纳曲酮微球注射期。每只犬注射了 1g微球〔纳曲酮 ( 2 3 .6± 1 .5 )mg·kg-1〕后 ,纳曲酮的血药浓度超过 1 μg·L-1达 2 6～ 2 8d ,单位剂量 (mg·kg-1)的cmax约为盐酸纳曲酮的 1 %。在4条犬体内 ,为( 93 .0± 4.1 ) %的剂量被吸收。除了轻微的炎症外 ,未发现严重的副作用。结论 通过本实验的初步研究表明该纳曲酮微球缓释制剂安全、稳定 ,完全地缓慢释放约 1个月。
AIM To evaluate bioavailability, biocompa tibility and biodegradability of an injectable microsphere sustained release preparation of naltrexone(NTX) in 4 dogs. METHODS Pharmacokinetic data of NTX and remained NTX in microspheres in injection site were studied using high performance liquid chromatography(HPLC) electrochemical detection with naloxone(NLX) as internal standard. Biocompatibility of the microspheres was assayed by histological examination. RESULTS Pharmacokinetics of NTX after an intramuscular dose of 0.5 or 1.0 mg·kg -1 NTX indicated a plasma clearance range of 0.66 to 0.73 L·min -1 and a t 1/2β range of 60.0 to 67.2 min. After a 1 week washout period without medication, NTX microspheres injection period about 4 weeks followed. After injection of 1.0 g of microspheres containing (296.5±2.1)mg of NTX, mean blood concentrations of NTX exceeded 1 μg·L -1 for 26-28 d, and c max per dose (mg·kg -1 ) was only 1% of that after NTX dosing. It was estimated that approximately (93.0±4.1)% of the administered dose was absorbed after microspheres injection in 4 dogs. There were no serious adverse effects other than light tissue irritation. CONCLUSION This NTX microspheres preparation provides a safe, complete and sustained release of the drug for about one month.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2003年第3期167-171,共5页
Chinese Journal of Pharmacology and Toxicology
关键词
纳曲酮
微球
缓释制剂
药代动力学
色谱法
高效液相
naltrexone
microspheres
sustained release preparation
pharmacokinetics
chromatography, high performance liquid
