甲磺酸桂哌齐特与马来酸桂哌齐特注射液药动学比较研究
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摘要
目的比较甲磺酸桂哌齐特与马来酸桂哌齐特注射液的药动学特征。方法 12名健康志愿者,按照2×2交叉试验设计分别静脉滴注甲磺酸桂哌齐特或马来酸桂哌齐特,连续5d,每日1次。给药后于规定时间采血并收集尿液。洗脱期为10d。结果甲磺酸桂哌齐特与马来酸桂哌齐特单次给药后t1/2分别为2.20±0.42和2.26±0.36h;AUC0~t分别为19.329±2.879和18.547±3.727μg·h·mL-1;Cmax分别为5.386±0.809和5.345±1.035μg·mL-1;CL分别为13.02±2.10和13.87±3.29L·h-1;24h内桂哌齐特(CPZ)尿累积排泄率分别为55.30%±3.39%和56.22%±3.61%。连续5d静脉滴注甲磺酸桂哌齐特与马来酸桂哌齐特后t1/2分别为2.18±0.33和2.52±0.50h;AUC0~t分别为20.168±3.178和18.750±1.763μg·h·mL-1;Cmax分别为5.541±0.520和5.426±0.730μg·mL-1;Cmin低于检测限;CL分别为12.52±1.94和13.21±1.17L·h-1;MRT0~t分别为3.53±0.24和3.56±0.20h。CPZ的主要药动学参数和尿累积排泄率在单次与多次给药间、不同酸根间差异均无统计学意义(P>0.05)。结论甲磺酸桂哌齐特与马来酸桂哌齐特在人体内药动学行为相似,连续多次给药,体内无蓄积。
Objective To compare the pharmacokinetic characteristics between cinepazide mesylate and cinepazide maleate.Methods12 healthy volunteers were given drips of cinepazide mesylate and cinepazide maleate intravenously once daily in 5 days according to the 2×2 crossover design.Blood and urine samples were collected from volunteers at different times after intravenous drip.Results In the single-dose study between cinepazide mesylate and cinepazide maleate,the main pharmacokinetic parameters of cinepazide were as follows:t1/2 were 2.20±0.42 and 2.26±0.36 h;AUC0-twere 19.329±2.879 and 18.547±3.727μg·h·mL-1;Cmaxwere5.386±0.809 and 5.345±1.035μg·mL-1;CL were 13.02±2.10 and 13.87±3.29 L·h-1;the average cumulative excretory rate of cinepazide(CPZ)in urine were 55.30%±3.39% and 56.22%±3.61%.After intravenous drip of cinepazide mesylate and cinepazide maleate for 5 days,the main pharmacokinetic parameters of cinepazide were as follows:t1/2 were 2.18±0.33 and 2.52±0.50 h;AUC0-twere 20.168±3.178 and 18.750±1.763μg·h·mL-1;Cmaxwere 5.541±0.520 and 5.426±0.730μg·mL-1;Cmin were not detected;CL were 12.52±1.94 and 13.21±1.17 L·h-1;MRT0-twere 3.53±0.24 and 3.56±0.20 h.The main parameters and the cumulative excretion rate of urine of cinepazide showed no significant difference(P>0.05)between the single and multiple doses or cinepazide mesylate and cinepazide maleate.Conclusion The pharmacokinetic process of cinepazide mesylate and cinepazide maleate was similar.Multiple doses of cinepazide had no drug accumulation in vivo.
Objective To compare the pharmacokinetic characteristics between cinepazide mesylate and cinepazide maleate.Methods12 healthy volunteers were given drips of cinepazide mesylate and cinepazide maleate intravenously once daily in 5 days according to the 2×2 crossover design.Blood and urine samples were collected from volunteers at different times after intravenous drip.Results In the single-dose study between cinepazide mesylate and cinepazide maleate,the main pharmacokinetic parameters of cinepazide were as follows:t1/2 were 2.20±0.42 and 2.26±0.36 h;AUC0-twere 19.329±2.879 and 18.547±3.727μg·h·mL-1;Cmaxwere5.386±0.809 and 5.345±1.035μg·mL-1;CL were 13.02±2.10 and 13.87±3.29 L·h-1;the average cumulative excretory rate of cinepazide(CPZ)in urine were 55.30%±3.39% and 56.22%±3.61%.After intravenous drip of cinepazide mesylate and cinepazide maleate for 5 days,the main pharmacokinetic parameters of cinepazide were as follows:t1/2 were 2.18±0.33 and 2.52±0.50 h;AUC0-twere 20.168±3.178 and 18.750±1.763μg·h·mL-1;Cmaxwere 5.541±0.520 and 5.426±0.730μg·mL-1;Cmin were not detected;CL were 12.52±1.94 and 13.21±1.17 L·h-1;MRT0-twere 3.53±0.24 and 3.56±0.20 h.The main parameters and the cumulative excretion rate of urine of cinepazide showed no significant difference(P>0.05)between the single and multiple doses or cinepazide mesylate and cinepazide maleate.Conclusion The pharmacokinetic process of cinepazide mesylate and cinepazide maleate was similar.Multiple doses of cinepazide had no drug accumulation in vivo.
引文
[1]赵宏伟,张晓荧,张四喜,等.马来酸桂哌齐特注射液的临床应用分析[J].中国药物应用与监测,2016,13(3):175-177.
[2]姚波,孙玉敏,武学伟,等.疏血通注射液联合桂哌齐特治疗短暂性脑缺血发作的疗效观察[J].现代药物与临床,2016,31(10):1595-1598.
[3]周智慧,杨杰.中药干预细胞能量代谢治疗心脑血管疾病的研究进展[J].西北药学杂志,2016,31(6):658-660.
[4]李昱,王冠涛,王洪有.马来酸桂哌齐特治疗不稳定型心绞痛的疗效观察[J].医学信息,2014,27(6):215-216.
[5]史楠,余波,于伟红,等.马来酸桂哌齐特对高血压性脑出血的临床研究[J].中国临床药理学杂志,2016,32(3):270-273.
[6]宫大勇.马来酸桂哌齐特联合尤瑞克林治疗急性脑梗死临床研究[J].现代药物与临床,2017,32(3):394-397.
[7]易湛苗,刘芳,翟所迪.马来酸桂哌齐特治疗急性脑梗塞的系统评价[J].中国循证医学杂志,2010,10(9):1079-1084.
[8]李青,杨卫忠,张国良,等.马来酸桂哌齐特治疗自发性蛛网膜下腔出血的疗效观察[J].海峡药学,2006,18(4):111-112.
[9]冯宇鹏,叶向东,连学雄,等.马来酸桂哌齐特治疗肾绞痛的临床疗效及安全性评价[J].中国临床药理学杂志,2015,31(18):1822-1824.
[10]陈立波,崔艳凤,张长宁,等.马来酸桂哌齐特治疗糖尿病肾病的临床观察[J].医学研究杂志,2016,45(12):141-143.
[11]韦丽,张建军.甲钴胺、依帕司他、马来酸桂哌齐特治疗糖尿病周围神经病变的效果[J].中国医药导报,2016,13(5):157-160.
[12]朱力华.马来酸桂哌齐特联合盐酸异丙嗪治疗急诊眩晕症的价值分析[J].当代医学,2017,23(1):71-72.
[13]李晋岗,张颖,罗芳梅,等.HPLC-MS/MS法研究人尿中甲磺酸桂哌齐特的主要代谢产物[J].中南药学,2014,12(8):782-785.
[14]刘华祥.马来酸桂哌齐特的制备及其光致顺反异构研究[D].大连:大连理工大学,2009.
[15]卢海儒,孙海霞.克林澳[J].中国新药杂志,2003,12(11):957-959.
[16]项燕凌.丹参酮ⅡA磺酸钠联合马来酸桂哌齐特治疗不稳定型心绞痛患者临床疗效观察[J].中国现代医学杂志,2015,25(9):51-53.
[17]刘永,王新玲.依达拉奉联合左旋氨氯地平治疗高血压脑梗死的疗效观察[J].西北药学杂志,2016,31(4):412-414.
[18]冯怡墨,孙晓川,张晓冬,等.依达拉奉联合马来酸桂哌齐特治疗动脉瘤性蛛网膜下腔出血后脑血管痉挛的临床观察[J].中国药房,2017,28(2):230-232.
[19]罗芳梅,何周康,王婷,等.甲磺酸桂哌齐特注射液在健康志愿者中的药动学研究[J].中南药学,2017,15(2):178-182.
[2]姚波,孙玉敏,武学伟,等.疏血通注射液联合桂哌齐特治疗短暂性脑缺血发作的疗效观察[J].现代药物与临床,2016,31(10):1595-1598.
[3]周智慧,杨杰.中药干预细胞能量代谢治疗心脑血管疾病的研究进展[J].西北药学杂志,2016,31(6):658-660.
[4]李昱,王冠涛,王洪有.马来酸桂哌齐特治疗不稳定型心绞痛的疗效观察[J].医学信息,2014,27(6):215-216.
[5]史楠,余波,于伟红,等.马来酸桂哌齐特对高血压性脑出血的临床研究[J].中国临床药理学杂志,2016,32(3):270-273.
[6]宫大勇.马来酸桂哌齐特联合尤瑞克林治疗急性脑梗死临床研究[J].现代药物与临床,2017,32(3):394-397.
[7]易湛苗,刘芳,翟所迪.马来酸桂哌齐特治疗急性脑梗塞的系统评价[J].中国循证医学杂志,2010,10(9):1079-1084.
[8]李青,杨卫忠,张国良,等.马来酸桂哌齐特治疗自发性蛛网膜下腔出血的疗效观察[J].海峡药学,2006,18(4):111-112.
[9]冯宇鹏,叶向东,连学雄,等.马来酸桂哌齐特治疗肾绞痛的临床疗效及安全性评价[J].中国临床药理学杂志,2015,31(18):1822-1824.
[10]陈立波,崔艳凤,张长宁,等.马来酸桂哌齐特治疗糖尿病肾病的临床观察[J].医学研究杂志,2016,45(12):141-143.
[11]韦丽,张建军.甲钴胺、依帕司他、马来酸桂哌齐特治疗糖尿病周围神经病变的效果[J].中国医药导报,2016,13(5):157-160.
[12]朱力华.马来酸桂哌齐特联合盐酸异丙嗪治疗急诊眩晕症的价值分析[J].当代医学,2017,23(1):71-72.
[13]李晋岗,张颖,罗芳梅,等.HPLC-MS/MS法研究人尿中甲磺酸桂哌齐特的主要代谢产物[J].中南药学,2014,12(8):782-785.
[14]刘华祥.马来酸桂哌齐特的制备及其光致顺反异构研究[D].大连:大连理工大学,2009.
[15]卢海儒,孙海霞.克林澳[J].中国新药杂志,2003,12(11):957-959.
[16]项燕凌.丹参酮ⅡA磺酸钠联合马来酸桂哌齐特治疗不稳定型心绞痛患者临床疗效观察[J].中国现代医学杂志,2015,25(9):51-53.
[17]刘永,王新玲.依达拉奉联合左旋氨氯地平治疗高血压脑梗死的疗效观察[J].西北药学杂志,2016,31(4):412-414.
[18]冯怡墨,孙晓川,张晓冬,等.依达拉奉联合马来酸桂哌齐特治疗动脉瘤性蛛网膜下腔出血后脑血管痉挛的临床观察[J].中国药房,2017,28(2):230-232.
[19]罗芳梅,何周康,王婷,等.甲磺酸桂哌齐特注射液在健康志愿者中的药动学研究[J].中南药学,2017,15(2):178-182.