磷酸川芎嗪缓释制剂在比格犬体内的药动学和生物等效性研究  

Pharmacokinetics and Bioequivalence of Tetramethylpyrazine Phosphate Sustained-release Preparations after Oral Administration in Beagle Dogs

作　　者：肖衍宇[1] 陈志鹏[2] 刘雯[1] 钱红艳[1] 平其能[1] 

机构地区：[1]中国药科大学药剂教研室,南京210009 [2]南京中医药大学药剂教研室,南京210046

出　　处：《中国药学杂志》2011年第17期1344-1348,共5页Chinese Pharmaceutical Journal

基　　金：国家重大新药创制科技重大专项(2009ZX09310-004);中央高校基本科研业务费专项资金资助(JKQ2009018)

摘　　要：目的研究自制磷酸川芎嗪(TMPP)缓释微丸及TMPP冰片复方缓释微丸与市售TMPP普通片在比格犬体内的单剂量和多剂量的药动学和生物等效性。方法利用高效液相-紫外检测6只比格犬单剂量与多剂量分别口服TMPP缓释微丸及TMPP冰片复方缓释微丸与市售TMPP普通片后的血药浓度,应用3P97程序计算药动学参数,对AUC0～∞、AUC0-24 h的对数值进行方差分析、双单侧t检验等统计学处理,以80%～125%为等效标准,评价缓释制剂与普通制剂的生物等效性。结果单剂量时TMPP缓释微丸的tmax、ρmax、AUC0～24 h和MRT分别为(2.50±0.29)h、(213.06±32.44)ng.mL-1、(2 722.25±369.42)ng.h.mL-1和(9.43±1.05)h,TMPP冰片复方缓释微丸的上述参数分别为(2±0.76)h、(252.09±28.96)ng.mL-1、(3 613.51±974.16)ng.h.mL-1和(9.14±2.56)h,市售普通片的上述参数分别为(0.33±0.09)h、(3 402.13±584.97)ng.mL-1、(2 801.24±560.17)ng.h.mL-1和(1.52±0.35)h。多剂量达稳态时TMPP缓释微丸的tmax、ρmax、ρmin、AUC0～24 h、ρav和FI分别为(2±0.12)h、(340.36±28.91)ng.mL-1、(60.39±11.18)ng.mL-1、(3 161.82±314.68)ng.h.mL-1、(145.94±15.68)ng.mL-1和(191.84±11.58)%,TMPP冰片复方缓释微丸的上述参数分别为(2±0.31)h、(402.21±29.48)ng.mL-1、(80.13±21.65)ng.mL-1、(4 025.17±954.76)ng.h.mL-1、(167.87±29.37)ng.mL-1和(191.87±13.29)%,市售普通片的上述参数分别为(0.5±0.011)h、(376.79±44.6)ng.mL-1、0 ng.mL-1、(2 550.27±154.88)ng.h.mL-1、(114.93±13.68)ng.mL-1和(327.84±22.37)%。结论经方差分析和双单侧t检验,不论是单剂量口服还是多剂量口服,TMPP缓释微丸和普通片均具有生物等效性,而TMPP复方缓释微丸与普通片均生物不等效。缓释制剂均表现出良好的缓释效果,且波动系数均优于普通片。OBJECTIVE To study the pharmacokinetics and bioequivalence of self-prepared tetramethylpyrazine phosphate （TMPP） sustained-release pellets, TMPP-borneol compound sustained-release pellets and TMPP conventional tablets after a single and multiple oral dose in beagle dogs. METHODS The plasma concentration of TMPP was measured by HPLC-UV. The pharmacokinetic parameters of the three preparations were calculated by 3P97 program. The LnAUC0-∞ or LnAUC0-24 h were used to evaluate the bioequivalence of the three preparations by analysis of variance and two one side t-test. RESULTS After a single dose administration of TMPP sustained-release pellets, the t P AUC0-24h and MRT were （2.50 ± 0.29）h, （213.06 ± 32.44）ng ·mL-1 （2 722. 25 ± 369.42） ng ·h·mL-1 and （9. 43 ± 1.05 ） h, respectively. For compound sustained-release pellets, the same pharmacokinetic parameters were（2 ±0. 76）h, （252. 09 ±28.96） ng ·mL-1 , （3 613.51 ±974. 16） ng·h·mL-1 and（9. 14 ±2. 56）h, respectively. For the conventional tablets, the same pharmacokinetic parameters were （0. 33 ± 0. 09 ） h, （3 402. 13 ± 584. 97 ） ng ·mL-1 , （2 801.24 ±560. 17）ng ·h·mL-1 and （ 1.52 ±0. 35）h, respectively. After multiple oral doses administration of TMPP sustained-release pellets, the steady state tamx、ρmax、AUC0-24h、ρav and FI were （2 ± 0. 12）h, （340. 36 ± 28. 91 ） ng ·mL-1, （60.39±11.18） ng·mL-1, （3 161.82±314.68） ng·h·mL-1, （145.94±15.68）ng·mL-1 and （191.84±11.58）%, respectively. For compound sustained-release pellets, the same pharmacokinetic parameters were （2 ± 0. 31 ） h, （402. 21 ± 29.48） ng ·mL-1 （80. 13 ±21.65）ng ·mL-1 （4025.17 ±954. 76）ng ·h·mL-1, （167.87 ±29. 37） ng·mL-1 and （191.87 ± 13.29）%, respectively. For the conventional tablets, the same pharmacokinetic parameters were （0. 5 ± 0. 011 ）h, （376. 79 ± 44. 6） ng·mL-1 0 ng ·mL-1, （2 550. 27 ± 154. 88 ）ng ·h·mL-1, （ 114. 93 ± 13.68 ） ng

关 键 词：磷酸川芎嗪 冰片 缓释微丸 药动学 生物等效性 

分 类 号：R969.1[医药卫生—药理学]