盐酸噻吩诺啡舌下喷雾剂的药效学及药动学评价  

Pharmcodynamics and Pharmcokinetics of Sublingual Spray Containing Thenorphine Hydrochloride

作　　者：刘霏[1,2] 刘玲[2] 高永良[2] 

机构地区：[1]中国人民解放军总医院第一附属医院药剂药理科,北京100037 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药学杂志》2010年第3期203-205,共3页Chinese Pharmaceutical Journal

摘　　要：目的对制备的盐酸噻吩诺啡舌下喷雾剂进行药效学、药动学评价,并计算舌下喷雾剂的绝对生物利用度。方法热板法考察盐酸噻吩诺啡于小鼠舌下、灌胃、皮下3种给药方式下的量效关系,计算ED50,ED80,ED95;并考察ED80剂量给药后的时效关系。采用LC-MS/MS测定舌下和静脉注射2种给药方式下大鼠体内的血药浓度,计算药动学参数和绝对生物利用度。结果药效学实验结果证明,本剂型起效快,药效明显优于灌胃给药,接近于皮下给药;药动学研究结果显示,舌下给药的tmax约为9 min,ρmax约为静注的1/2,t1/22种给药方式无显著性差异。大鼠体内绝对生物利用度达到58.48%。结论盐酸噻吩诺啡舌下喷雾剂起效迅速,绝对生物利用度高,具有很好的应用前景。OBJECTIVE To study pharmcodynamics and pharmacokinetics of nasal spray containing thenorphine hydrochloride. METHODS The pharmacodynamic action of the spray was studied with hot plate test and compared with that of the drug administrated by sc and ig to evaluate the analgesic effect in mice. Wistar rats were given 3 mg·kg^-1 thenorphine hydrochloride intravenoush and sublingually, respectively. Drug plasma concentration was determined by LC-MS/MS. Pharmacokinetie parameters were evaluated, and the absolute bioavailability was also calculated. RESULTS The sublingual spray produced quicker and better effect than intragastric administration at the same dose. Pharmcokinctic study showed that the absolute bioavailability of sublingual spray of thenorphine hydrochlride was 58.48% in wistar rats. CONCLUSION The sublingual spray of thenorphine hydrochloride developed in this study was confirmed with quick absorption and high relative bioavailability.

关 键 词：盐酸噻吩诺啡 舌下喷雾剂 药效学 热板法 液相色谱-质谱联用法 药动学 生物利用度 

分 类 号：R944[医药卫生—药剂学] R969.1[医药卫生—药学]