盐酸丁螺环酮凝胶喷鼻剂在大鼠体内的药动学性质考察  

Pharmacokinetic properties of buspirone hydrochloride gel spray after nasal administration in rats

作　　者：刘昕[1] 张晶[2] 武凤兰[1] 

机构地区：[1]北京大学药学院,北京100083 [2]北京化工大学生命科学与技术学院,北京100029

出　　处：《中国新药杂志》2008年第5期383-388,共6页Chinese Journal of New Drugs

摘　　要：目的:对盐酸丁螺环酮凝胶喷鼻剂在大鼠体内的药动学性质进行考察,评价其作为鼻腔给药系统的应用价值。方法:将15只大鼠随机分为3组,分别进行静脉给药、灌胃给药及鼻腔给药,剂量均为10mg·kg-1,颈动脉取血后用HPLC法测定各时间点血浆中盐酸丁螺环酮及其活性代谢物1-(2-嘧啶基)哌嗪的浓度,用3P87程序软件处理后,以t检验对药动学参数进行显著性检验。结果:鼻腔给药组活性代谢物1-(2-嘧啶基)哌嗪的AUC值与静脉给药组比较,差异无统计学意义[(506.19±59.35)vs(522.14±108.90)nmol·mL-1.min,P>0.05];但显著低于灌胃给药组[(506.19±59.35)vs(716.70±67.10)nmol.mL-1.min,P<0.05]。盐酸丁螺环酮大鼠鼻腔给药吸收快,其绝对生物利用度为(83.71±7.66)%,相对于灌胃给药的生物利用度为(2039.74±186.77)%。结论:盐酸丁螺环酮鼻腔给药可以显著提高口服给药的生物利用度,有望制成凝胶喷鼻剂。Objective ： To investigate the practicability of buspirone hydrochloride gel spray as a nasal drug delivery system, we observed its pharmacokinetics in rats. Methods： Fifteen rats were randomly divided into three groups. The fate of drug in the plasma of rats was monitored after intravenous, intragastric and intranasal administration of buspirone hydrochloride 10 mg·kg^-1. The concentrations of parent drug and its active metabolite 1-（2- pyrimidinyl） piperazine （1-PP） in plasma were determined by HPLC with UV detection. The concentration-time data were analyzed using 3P87 pharmacokinetic program, and the pharmacokinetic parameters were compared by ttest. Results： The AUC value of the active metabolite 1-PP was （506.19 ±59.35） nmol·mL^-1·min after intranasal administration, which was similar to that after intravenious administration [ （522.14± 108.90）nmol·mL^-1· min,P 〉 0. 05 ] but was significantly smaller than that after intragastric administration [ （716.70 ± 67.10） nmol·mL^-1·min, P 〈0. 05 ]. Buspirone hydrochloride after intranasal administration was absorbed fast. Its absolute bioavailability was （83.71 ±7.66）.%, and the relative bioavailability was up to （2 039.74 ± 186.77） % in comparison with intragastric administration. Conclusion： The bioavailability of buspirone hydrochloride gel spray can be significantly increased after nasal administration, which may be an effective preparation as nasal drug delivery system.

关 键 词：盐酸丁螺环酮 活性代谢物 凝胶喷鼻剂 药动学 

分 类 号：R944.9[医药卫生—药剂学] R971.4[医药卫生—药学]