目的 研究羟基红花黄色素A油包水型纳米乳(hydroxysafflor yellow A nanoemulsion,HYAN)在大鼠体内的药动学行为,并比较HYAN与羟基红花黄色素A(hydroxysafflor yellow A,HSYA)的生物等效性。方法 将12只雄性SD大鼠随机分成2组,分别灌胃给予HSYA或HYAN,给药后不同时间点大鼠眼底静脉丛采血,采用HPLC测定HSYA的血药浓度。结果 HYAN的主要药动学参数为:药-时曲线下面积(AUC0-24 h)、峰浓度、达峰时间和血浆清除率分别为(31.56±4.58)mg·h·L-1、(12.75±2.64)mg·L-1、(0.83±0.54)h和(1.89±0.93)L·h-1·kg-1。相对于HSYA,HYAN的AUC0-24 h、ρmax和tmax分别提高了4.76、9.20和1.52倍,且HYAN的CL仅为HSYA的1/4。AUC0-24 h和ρmax的90%置信区间均不在所规定的生物等效性标准区间范围内。结论 相对于HSYA,HYAN在体内血药浓度高且达峰时间延长,可以明显提高HSYA的口服生物利用度,且两者生物不等效。
Abstract
OBJECTIVE To study the pharmacokinetics and bioequivalence of hydroxysafflor yellow A (HSYA) and hydroxysafflor yellow A nanoemulsion (HYAN) in rats.METHODS Twelve male rats were randomly divided into two groups. The rats were administered intragastrically with HSYA or HYAN, respectively, and then blood was collected from the venous plexus at different time points. HPLC method was used for the determination of HSYA blood concentration.RESULTS The main pharmacokinetic parameters of HYAN were as follows: the area under curve (AUC0-24 h), peak concentration (ρmax), peak time (tmax) and clearance (CL) were (31.56±4.58) mg·L·h-1, (12.75±2.64) mg·L-1, (0.83±0.54) h and (1.89±0.93) L·h-1·kg-1, respectively. The AUC0-24 h, ρmax and tmax of HYAN increased by 5.49, 10.22 and 2.50 times, respectively, and the CL of HYAN was only 1/4 of that of HSYA. The 90% confidence intervals for AUC0-24 h and ρmax were not within the prescribed range of bioequivalence criteria.CONCLUSION Relative to HSYA, the high plasma concentration and prolonged peak time of HYAN in vivo can significantly improve the oral bioavailability of HSYA. HSYA solution and HYAN are not bioequivalent.
关键词
羟基红花黄色素A /
纳米乳 /
高效液相色谱法 /
药动学 /
生物等效性
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Key words
hydroxysafflor yellow A /
nanoemulsion /
high performance liquid chromatography /
pharmacokinetics /
bioequivalence
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中图分类号：
R944
R969.1
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参考文献
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脚注
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基金
重庆市科委资助项目(cstc2017shmsA0174);重庆市研究生科研创新项目资助(CYS17172)
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