不同剂型琥珀酸美托洛尔在大鼠体内的药代动力学对比研究
|
摘要
目的研究琥珀酸美托洛尔普通颗粒与自制缓释微丸的药代动力学行为,并验证缓释微丸的缓释特性,为后期开展缓释制剂研究打下基础。方法将大鼠随机分为普通组、缓释组各6只,每组雌雄各3只,普通组大鼠单次口服琥珀酸美托洛尔普通颗粒,缓释组大鼠单次口服等剂量的琥珀酸美托洛尔缓释微丸。采用LC-MS/MS法测定血药浓度,采用DAS 2.1.1版药代动力学软件计算药代动力学参数,采用SPSS13.0统计学软件进行统计学分析。结果结果表明,两种剂型的AUC(0-t)、AUC(0-∞)、Cmax以及MRT(0-t)、MRT(0-∞)、t1/2z、Tmax差异显著,具有统计学意义。结论琥珀酸美托洛尔自制缓释微丸具有显著的缓释特性。可为新剂型的研制、开发提供资料参考。
Objective To study the succinic acid metoprolol ordinary particles with homemade slow-release the pharmacokinetic behavior of micro pill,verify that slow release characteristics of slow release micro pill and lay the foundation for later research on sustained-release preparations.Methods Rats were randomly divided into normal group,lowdose group,each group of male and female 3only.The normal group was tresated with single oral metoprolol succinic acid in rats of ordinary particles.The slow-release group was treated with a single oral dose of succinic acid such as metoprolol sustained-release micro pill.The LC-MS/MS method was used to detect the blood drug concentration.ResultsStatistical results shown that the two formulations of AUC(0-t),AUC(0-up),Cmax and the MRT(0-t)and the MRT(0-up),t1/2z,Tmax were significantly different.Conclusion Homemade succinate metoprolol sustained-release micro pill has significant sustained release characteristics.
Objective To study the succinic acid metoprolol ordinary particles with homemade slow-release the pharmacokinetic behavior of micro pill,verify that slow release characteristics of slow release micro pill and lay the foundation for later research on sustained-release preparations.Methods Rats were randomly divided into normal group,lowdose group,each group of male and female 3only.The normal group was tresated with single oral metoprolol succinic acid in rats of ordinary particles.The slow-release group was treated with a single oral dose of succinic acid such as metoprolol sustained-release micro pill.The LC-MS/MS method was used to detect the blood drug concentration.ResultsStatistical results shown that the two formulations of AUC(0-t),AUC(0-up),Cmax and the MRT(0-t)and the MRT(0-up),t1/2z,Tmax were significantly different.Conclusion Homemade succinate metoprolol sustained-release micro pill has significant sustained release characteristics.
引文
[1]孙畅,张春敏,罗武奎,等.琥珀酸美托洛尔缓释片治疗慢性充血性心力衰竭的临床效果观察[J].中国实用医药,2016,11(34):106-108.
[2]谢向阳,邢传峰,李银科,等.琥珀酸美托洛尔缓释微丸片剂的制备与体外释放度考察[J].解放军药学报,2014,30(4):299-302.
[3]王倩英.酒石酸美托洛尔与琥珀酸美托洛尔治疗扩张型心肌病效果比较[J].河南医学研究,2016,25(9):1682-1683.
[4]李后涛,厉保秋,黄桂华,等.两种美托洛尔缓释片在比格犬体内的药代动力学对比研究[J].药学研究,2014,33(1):5-8.
[5] Zhao WG,Gui J.The effects of-blockers metoprolol succinate on chronic heart failure[J].China Pract Med,2009,4(27):58-59.
[6]汪宇星,孙敏捷,平其能,等.琥珀酸美托洛尔缓释微丸的制备及大鼠体内药代动力学[J].中国药科大学学报,2013,44(4):334-338.
[7]代静静,钱勇,张应辉,等.星点设计-效应面法优化琥珀酸美托洛尔缓释微丸处方[J].军事医学,2014,5:351-354.
[8]丁斌,刘阿敏,李德刚,等.琥珀酸S-美托洛尔缓释片的研制及体外释放特征探讨[J].安徽医药,2015,19(4):651-655.
[9]王曦林,余海清,舒红利,等.琥珀酸美托洛尔缓释片的制备及释放度研究[J].中国处方药,2016,14(3):8-9.
[10]蒋鸣,刘汗清,谢涛.中药缓释制剂的研究进展[J].中国医药导报,2010,5:9-11.
[11]赵春宝,江蔚新,程斌,等.口服中药缓释制剂组分释放同步性的研究进展[J].中国实验方剂学杂志,2015,21(3):213-216.
[12]杨萍,全姬善.口服缓释制剂的研究进展[J].药学研究,2017,36:44-47.
[13]佟婉红,刘钰.缓释制剂的剂型特点及用药方法[J].甘肃医药,2012,31(3):219-220.
[14]姬小婷,李凤,魏虹,等.黄芩苷和牛血清蛋白双缓释制剂的制备及释药性能检测[J].口腔生物医学,2012,3(2):57-60.
[15]陈亚军,王淑君,汪珊珊,等.UPLC法测定大鼠血浆中藤黄酸葡萄糖酯及其药代动力学研究[J].中药临床药理学与治疗学,2015,50(4):374-378.
[16] Marucei M,Ragnarsson G,Corswant C,et al.Polymer leaching from film coating:effects on the coating transport properties[J].Int J Pharm,2011,411(1/2):43-48.
[17] Kranz H,Gutsche S.Evaluation of the drug release patterns and long term stability of aqueous and organic coated pellects by using blends of enteric and gastrointestinal insoluble polymers[J].Int J Pharm,2009,380(1/2):112-119.
[18]樊玲,李洁,彭兆亮,等.UPLC分析大鼠血浆中阿齐沙坦浓度及其初步药代动力学研究[J].安徽中医药大学学报,2016,36(1):77-80.
[19] Cuppok Y,Muschert S,Marucci M,et al.Drug release mechanisms from Kollicoat SR:Eud ragit NE coated pellects[J].Int J Pharm,2011,409(1/2):30-37.
[20]张华,徐荣.琥珀酸美托洛尔缓释片的制备与含量测定[J].医药导报,2016,35(8):870-874.
[2]谢向阳,邢传峰,李银科,等.琥珀酸美托洛尔缓释微丸片剂的制备与体外释放度考察[J].解放军药学报,2014,30(4):299-302.
[3]王倩英.酒石酸美托洛尔与琥珀酸美托洛尔治疗扩张型心肌病效果比较[J].河南医学研究,2016,25(9):1682-1683.
[4]李后涛,厉保秋,黄桂华,等.两种美托洛尔缓释片在比格犬体内的药代动力学对比研究[J].药学研究,2014,33(1):5-8.
[5] Zhao WG,Gui J.The effects of-blockers metoprolol succinate on chronic heart failure[J].China Pract Med,2009,4(27):58-59.
[6]汪宇星,孙敏捷,平其能,等.琥珀酸美托洛尔缓释微丸的制备及大鼠体内药代动力学[J].中国药科大学学报,2013,44(4):334-338.
[7]代静静,钱勇,张应辉,等.星点设计-效应面法优化琥珀酸美托洛尔缓释微丸处方[J].军事医学,2014,5:351-354.
[8]丁斌,刘阿敏,李德刚,等.琥珀酸S-美托洛尔缓释片的研制及体外释放特征探讨[J].安徽医药,2015,19(4):651-655.
[9]王曦林,余海清,舒红利,等.琥珀酸美托洛尔缓释片的制备及释放度研究[J].中国处方药,2016,14(3):8-9.
[10]蒋鸣,刘汗清,谢涛.中药缓释制剂的研究进展[J].中国医药导报,2010,5:9-11.
[11]赵春宝,江蔚新,程斌,等.口服中药缓释制剂组分释放同步性的研究进展[J].中国实验方剂学杂志,2015,21(3):213-216.
[12]杨萍,全姬善.口服缓释制剂的研究进展[J].药学研究,2017,36:44-47.
[13]佟婉红,刘钰.缓释制剂的剂型特点及用药方法[J].甘肃医药,2012,31(3):219-220.
[14]姬小婷,李凤,魏虹,等.黄芩苷和牛血清蛋白双缓释制剂的制备及释药性能检测[J].口腔生物医学,2012,3(2):57-60.
[15]陈亚军,王淑君,汪珊珊,等.UPLC法测定大鼠血浆中藤黄酸葡萄糖酯及其药代动力学研究[J].中药临床药理学与治疗学,2015,50(4):374-378.
[16] Marucei M,Ragnarsson G,Corswant C,et al.Polymer leaching from film coating:effects on the coating transport properties[J].Int J Pharm,2011,411(1/2):43-48.
[17] Kranz H,Gutsche S.Evaluation of the drug release patterns and long term stability of aqueous and organic coated pellects by using blends of enteric and gastrointestinal insoluble polymers[J].Int J Pharm,2009,380(1/2):112-119.
[18]樊玲,李洁,彭兆亮,等.UPLC分析大鼠血浆中阿齐沙坦浓度及其初步药代动力学研究[J].安徽中医药大学学报,2016,36(1):77-80.
[19] Cuppok Y,Muschert S,Marucci M,et al.Drug release mechanisms from Kollicoat SR:Eud ragit NE coated pellects[J].Int J Pharm,2011,409(1/2):30-37.
[20]张华,徐荣.琥珀酸美托洛尔缓释片的制备与含量测定[J].医药导报,2016,35(8):870-874.