磷酸川芎嗪不同给药方式在大鼠体内药代动力学的研究
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摘要
目的研究磷酸川芎嗪(tetramethylpyrazine phosphate,TMPP)凝胶膏剂、片剂及注射剂在大鼠体内药动学差异。方法将18只SD大鼠随机分为凝胶膏剂组、口服给药组及静脉注射组,每组各6只。采用高效液相色谱法(HPLC)内标法测定不同时间点3组大鼠体内血药浓度,采用DAS 3.0软件计算各组药动学参数,并采用t检验和Wilcoxon秩和检验进行统计分析。结果 TMPP凝胶膏剂的AUC_(0-t)分别是片剂及注射剂的1.4倍和2.6倍,t_(1/2)分别是片剂及注射剂的8.6倍和4.1倍,平均滞留时间、达峰时间与片剂和注射剂相比,差异有统计学意义(P<0.05),血药浓度释放平稳。结论 TMPP凝胶膏剂能够降低血药浓度波动,具有一定缓释作用,值得进一步研究开发。
Objective To study the pharmacokinetic differences of tetramethylpyrazine phosphate(TMPP gel ointment,tablets and injections in rats.Methods A total of 18 SD rats were randomly divided into the gel ointment group,oral administration group and intravenous injection group,and each group consisted of 6 rats.The rats' plasma concentrations of the three groups at different time points were determined by the internal standard method of high performance liquid chromatography(HPLC).The pharmacokinetic parameters of each group were calculated by the software DAS 3.0 and the statistical analysis was performed by t test and Wilcoxon rank sum test.Results The AUC_(0-t) of TMPP gel ointment was 1.4 times and 2.6 times as much as that of tablets and injections respectively,and its t_(1/2) was 8.6 times and 4.1 times as much as that of tablets and injections respectively.The mean residence time and peak time of TMPP gel ointment were significantly different with the steady release of the plasma concentration when compared with those of tablets and injections(P<0.05).Conclusion TMPP gel ointment could reduce the fluctuation of plasma concentrations with a certain sustained-release effect,so it is worthy of further research and development.
Objective To study the pharmacokinetic differences of tetramethylpyrazine phosphate(TMPP gel ointment,tablets and injections in rats.Methods A total of 18 SD rats were randomly divided into the gel ointment group,oral administration group and intravenous injection group,and each group consisted of 6 rats.The rats' plasma concentrations of the three groups at different time points were determined by the internal standard method of high performance liquid chromatography(HPLC).The pharmacokinetic parameters of each group were calculated by the software DAS 3.0 and the statistical analysis was performed by t test and Wilcoxon rank sum test.Results The AUC_(0-t) of TMPP gel ointment was 1.4 times and 2.6 times as much as that of tablets and injections respectively,and its t_(1/2) was 8.6 times and 4.1 times as much as that of tablets and injections respectively.The mean residence time and peak time of TMPP gel ointment were significantly different with the steady release of the plasma concentration when compared with those of tablets and injections(P<0.05).Conclusion TMPP gel ointment could reduce the fluctuation of plasma concentrations with a certain sustained-release effect,so it is worthy of further research and development.
引文
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[11]Meng D M,Lu H Y,Huang S S,et al.Comparative pharmacokinetics of tetramethylpyrazine phosphate in rat plasma and extracellular fluid of brain after intranasal,intragastric and intravenous administration[J].Acta Pharm Sin B,2014,4(1):74-78.
[12]周晖,王东凯.α细辛脑巴布剂的家兔相对生物利用度研究[J].中国现代应用药学,2008,25(4):273-275.
[2]姜宇懋,王丹巧.川芎嗪药理作用研究进展[J].中国现代中药,2016,18(10):1364-1370.
[3]王丽,吕圭源,陈素红.川芎嗪药理作用的研究进展[J].医学信息(上旬刊),2011,24(2):1116-1118.
[4]刘立群,崔晓兰,曲韵智.磷酸川芎嗪制剂研究概况[J].北方药学,2013,10(1):40-41.
[5]夏红英,熊欣,涂明珠,等.磷酸川芎嗪滴丸溶出度测定方法的研究[J].中国药学杂志,2017,52(23):2117-2121.
[6]Xiao Y N,Ping Q N,Su Z G,et al.Preparation and pharmacokinetics in beagle dogs of once-a-day tetramethylpyrazine phosphate sustained-release pellets[J].Drug Dev Ind Pharm,2012,38(3):301-306.
[7]晏菲,马云淑,张惠玲,等.磷酸川芎嗪贴剂对大鼠心肌缺血的影响[J].华西药学杂志,2015,30(4):419-421.
[8]Qi X H,Liu R R,Sun D X,et al.Convolution method to predict drug concentration profiles of 2,3,5,6-tetramethylpyrazine following transdermal application[J].Int J Pharm,2003,259(1/2):39-45.
[9]罗红梅,马云淑,黄金娥,等.丁香挥发油对磷酸川芎嗪贴剂的经皮促渗作用[J].中国实验方剂学杂志,2012,18(11):40-43.
[10]张蜀,林华庆,邓红.磷酸川芎嗪缓释透皮贴剂的制备及体外释放度测定[J].药品评价,2005,2(4):292-294.
[11]Meng D M,Lu H Y,Huang S S,et al.Comparative pharmacokinetics of tetramethylpyrazine phosphate in rat plasma and extracellular fluid of brain after intranasal,intragastric and intravenous administration[J].Acta Pharm Sin B,2014,4(1):74-78.
[12]周晖,王东凯.α细辛脑巴布剂的家兔相对生物利用度研究[J].中国现代应用药学,2008,25(4):273-275.