盐酸纳洛酮鼻喷剂药动学及生物利用度研究  

Pharmacokinetic and absolute bioavailability study of naloxone hydrochloride nasal sprays

作　　者：刘亚琴[1,2] 孙建绪[1] 张晓燕[1] 高永良[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]国家发展改革委药品价格评审中心,北京100045

出　　处：《中国新药杂志》2010年第8期718-721,728,共5页Chinese Journal of New Drugs

摘　　要：目的:研究盐酸纳洛酮鼻喷剂在比格犬体内的药动学及生物利用度。方法:采用高效液相色谱法测定血浆中药物浓度;采用两周期交叉试验设计用于药物在比格犬体内的药动学及生物利用度研究。结果:盐酸纳洛酮在5～320 ng.mL-1范围内线性关系良好(r=0.999),样品方法回收率在87%～97%,绝对回收率71%～85%,日内和日间RSD均<9%。盐酸纳洛酮鼻喷剂的体内过程符合二室模型,主要的药动学参数为:Tmax=10 min,Cmax=(279.49±38.48)ng.mL-1,t1/2β=(176.94±30.14)min,CL×104=(5.48±0.77)mL.min-1,AUC0～12h=(14 495.00±2 029.38)ng.min.mL-1,AUC0～∞=(15 749.63±2 177.48)ng.min.mL-1;绝对生物利用度为(87.88±6.37)%。结论:盐酸纳洛酮鼻喷剂鼻腔吸收迅速,绝对生物利用度较高。Objective：To study the pharmacokinetics and bioavailability of naloxone hydrochloride nasal sprays in dogs.Methods：The HPLC method was developed to determine the concentration of naloxone hydrochloride in plasma.The two-period cross-over design was developed to study the pharmacokinetic and bioavailability of naloxone hydrochloride nasal sprays in dogs.Results：Good linearity was obtained in the range of 5~320 ng·mL-1（r=0.999）.The method recovery was 87%~97%.The absolute recovery was 71%~85%.Both of the intra-day and inter-day RSDs were less than 9%.The concentration-time curve of naloxone hydrochloride nasal sprays was consistent with the two-compartment model.The main pharmacokinetic parameters were as follows：Tmax 10 min,Cmax（279.49±38.48） ng·mL-1,t1/2β（176.94±30.14） min,CL×104（5.48±0.77） mL·min-1,AUC0~12h（14 495.00±2 029.38）ng·min·mL-1,AUC0~∞（15 749.63±2 177.48） ng·min·mL-1.The absolute bioavailability of naloxone hydrochloride nasal sprays in dogs was（87.88±6.37）%.Conclusion：Naloxone hydrochloride can be absorbed quickly after intranasal administration in dogs and the absolute bioavailability of Naloxone hydrochloride is high.

关 键 词：盐酸纳洛酮 鼻喷剂 高效液相色谱法 药动学 生物利用度 

分 类 号：R969.11[医药卫生—药理学] R979.3[医药卫生—药学]