摘要
建立了液相色谱-串联质谱法测定Beagle犬血浆中的氢溴酸加兰他敏。采用三周期单剂量随机交叉试验,以氢溴酸加兰他敏缓释胶囊(Razadyne ER)为参比制剂,研究了加兰他敏缓释混悬液(受试制剂)在进食与空腹状态下Beagle犬体内的药动学。6条Beagle犬分为3组,2组为进食组,1组为空腹组。进食组Beagle犬分别单剂量口服给予受试和参比制剂(剂量为10 mg,以加兰他敏氢溴酸盐计),空腹组给予等剂量受试制剂。上述3组的主要药动学参数为:t max(3.3±1.0)、(3.2±1.0)和(2.2±0.4)h,c max(63.0±3.4)、(69.5±6.2)和(65.1±12.0)ng/ml,t1/2(6.8±0.7)、(5.6±0.7)和(5.1±2.1)h,AUC0?t(633.5±38.3)、(657.2±76.9)和(557.1±36.7)ng·ml-1·h,AUC0?∞(691.5±34.8)、(698.1±81.3)和(595.9±70.4)ng·ml-1·h,MRT(7.5±0.1)、(7.3±0.6)和(6.9±0.8)h。
A LC-MS/MS method was established for the determination of galantamine hydrobromide in Beagle dog plasma. According to a three period crossover study, the feeding and fasting pharmacokinetics of galantamine sustained-release suspension （test preparation） in Beagle dogs were studied with galantamine hydrobromide sustainedrelease capsules （Razadyne ER） as the reference preparation. Six Beagle dogs were divided into three groups, two groups were in fed state and another was in fasting state. Dogs in fed groups were given a single dose of test or reference preparation at the dosage of 10 mg galantamine hydrobromide, and dogs in fasting group were given test preparation at the same dosage. The main pharmacokinetic parameters of above three groups were as follows： tmax （3.3±1.0）, （3.2±1.0） and （2.2±0.4）h, cmax （63.0±3.4）, （69.5±6.2） and （65.1±12.0）ng/ml, t1/2 （6.8±0.7）, （5.6±0.7） and （5.1±2.1）h, AUC0→t （633.5±38.3）, （657.2±76.9） and （557.1±36.7）ng·ml-1·h, AUC0→∞ （691.5±34.8）, （698.1±81.3） and （595.9±70.4）ng·ml-1·h, MRT （7.5±0.1）, （7.3±0.6） and （6.9±0.8）h, respectively.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2013年第12期1253-1257,共5页
Chinese Journal of Pharmaceuticals
基金
国家"重大新药创制"科技重大专项(2012ZX09304-004)
