盐酸氨溴索注射剂稳定性及体内药物动力学的深层次评价  

In-depth evaluation of stability and in vivo pharmacokinetics of Ambroxol Hydrochloride Injections

作　　者：张秀磊[1] 钱江辉 任筱青[1] 沙先谊[1] 

机构地区：[1]复旦大学,上海201203

出　　处：《中国药物经济学》2016年第11期11-16,共6页China Journal of Pharmaceutical Economics

摘　　要：目的深层次评价四种盐酸氨溴索注射剂在生理环境p H条件下的稳定性及体内药物动力学。方法以p H 7.4磷酸缓冲液模拟血液的生理p H环境,考察四种制剂不同剂量下与其混合后的含量和p H变化;采用随机、自身交叉试验设计,应用HPLC-MS/MS测定盐酸氨溴索血浆浓度,考察四种盐酸氨溴索制剂在比格犬体内的药物动力学。结果 A与B两种盐酸氨溴索注射水针剂在p H 7.4磷酸缓冲液中相对比较稳定;C和D两种注射用盐酸氨溴索粉针剂在低剂量时含量呈现下降趋势,高剂量时含量降低大于10%。四种制剂的缓冲能力具有明显的差别,水针剂的缓冲能力明显强于粉针剂。中、高剂量C、D制剂的生物利用度均明显低于A制剂,提示盐酸氨溴索注射剂配方的差异可能影响药物的生物利用度。四种制剂的药物生物半衰期t1/2随剂量的增加而改变,AUC(0-∞)随剂量增加呈现非线性增加的趋势,表明该药物体内动力学可能为非线性药物动力学过程。结论盐酸氨溴索水针剂配方中的缓冲盐体系增强了盐酸氨溴索对于PBS的稳定性,有利于提高药物在体内的稳定性。Objective To deep evaluate stability and pharmacokinetics of four ambroxol hydrochloride injections at physiological p H.Methods p H 7.4 phosphate buffer solution（PBS） was used to simulate physiological p H of blood, and the content and p H change of four preparations were measured after mixed with p H7.4 PBS at different dosages. The plasma concentration of ambroxol hydrochloride was determined by HPLC-MS/MS,and pharmacokinetics of four ambroxol hydrochloride preparations in beagle dogs were investigated by randomized,self-crossed design.Results In p H 7.4 PBS,A and B two ambroxol hydrochloride water injection were relatively stable;for C and D two powder injection of ambroxol hydrochloride for injection, content decreased at low-dose, and decreased more than 10% at high-dose.The buffering ability of four preparations was obviously different,and buffering ability of water injection was obviously stronger than that of powder injection.The bioavailability of C and D preparations in medium and high doses was significantly lower than that of A preparation, suggesting that differences in formulation of ambroxol hydrochloride injection may affect bioavailability of drug.The biological half-life t1/2 of four preparations changed with increasing dose, and AUC（0-∞） showed a nonlinear increased trend with increasing dose,indicating that pharmaco- kinetics of drug may be nonlinear pharmacokinetic processes.Conclusion The stability of ambroxol hydrochloride in PBS was enhanced by addition of buffer system in formulation of ambroxol hydrochloride injection,which was beneficial to improve in vivo stability of drug.

关 键 词：盐酸氨溴索 缓冲能力 HPLC-MS/MS 生物利用度 质量评价 

分 类 号：R927.11[医药卫生—药学]