目的 考察羟基红花黄色素A(hydroxysafflor yellow A,HSYA)在大鼠体内的线性动力学特征。方法 将18只雄性SD大鼠随机分成3组,以给药剂量30、60和120 mg·kg-1分别灌胃给予HSYA,给药后按预设时间点于大鼠眼底静脉丛取血,采用HPLC测定HSYA的血药浓度,运用描述法和置信区间法分析HSYA在大鼠体内的线性动力学特征。结果 HSYA的非房室模型和房室模型药动学参数清除率(clearance,CL)均在6 L·h-1·kg-1左右,无剂量依赖性,且血药浓度-时间曲线下面积(area under concentration-time curve,AUC)和峰浓度(peak concentration, ρmax)均与给药剂量呈线性关系。结论 30~120 mg·kg-1内HSYA在SD大鼠体内呈现线性动力学过程。
Abstract
OBJECTIVE To investigate the linear pharmacokinetics characteristics of hydroxysafflor yellow A (HSYA) in rats at different doses. METHODS Eighteen male SD rats were randomly divided into three groups. HSYA was administered intragastrically at doses of 30, 60 and 120 mg·kg-1 respectively. The blood samples were collected from rat fundus venous plexus at preset time points. The blood concentration of HSYA was determined by HPLC. The pharmacokinetic characteristics of HSYA in rats were analyzed by descriptive method and confidence interval method. RESULTS There were no dose dependence of non-atrioventricular and atrioventricular pharmacokinetic parameters clearance (CL), which were about 6 L·h-1·kg-1. The area under concentration-time curve (AUC) and peak concentration (ρmax) were correlated with the dosage of HSYA. CONCLUSION The pharmacokinetic parameters AUC of HSYA in the dose range of 30-120 mg·kg-1 have linear kinetic characteristics.
关键词
羟基红花黄色素A /
线性药动学 /
高效液相色谱法 /
描述法 /
置信区间法
{{custom_keyword}} /
Key words
hydroxysafflor yellow A /
linear pharmacokinetics /
high performance liquid chromatography /
description method /
confidence interval method
{{custom_keyword}} /
中图分类号：
R969.1
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] LU W D, ZHANG J Q. Biopharmaceutics and Pharmacokinetics(生物药剂学与药物动力学) [M]. Vol 1. Beijing: Science Press, 2017:204-220.
[2] HUMMEL J, MCKENDRICK S, BRINDLEY C, et al. Exploratory assessment of dose proportionality: review of current approaches and proposal for a practical criterion. Pharm Stat, 2009, 8(1):38-49.
[3] TIAN Y, YANG Z F, YANG J, et al. Pharmacokinetics of hydroxysafflower yellow A in healthy volunteers.Chin Pharm J (中国药学杂志), 2009, 44(10):781-783.
[4] YE X, KONG W, ZAFAR M I, et al. Serum triglycerides as a risk factor for cardiovascular diseases in type 2 diabetes mellitus: a systematic review and Meta-analysis of prospective studies. Cardiovasc Diabetol, 2019, 18(1):48.
[5] SHI M X, GUO Q, HUANG Y R, et al. Pharmacokinetics of hydroxysafflor yellow A nanoemulsion water-in-oil. Chin Pharm J (中国药学杂志), 2018, 53(24):2108-2112.
[6] ZHAO B, GU S, DU Y, et al. Solid lipid nanoparticles as carriers for oral delivery of hydroxysafflor yellow A. Int J Pharm, 2018, 535(1-2):164-171.
[7] QIAN X D, LV G Y, YUAN Y M, et al. Hydroxysafflower yellow A protects PC12 cells from injury induced by hypoxia, hypoglycemia and reperfusion and its effect on matrix metalloproteinase-9. Chin Pharm J (中国药学杂志),2013,48(9):691-695.
[8] JIN P H. Medical Statistical Method (医用统计方法) [M]. Vol 2. Shanghai: Shanghai Medical University Press, 1993:128-131.
[9] WANG J M, ZOU T, ZHANG Y Y, et al. Study on plasma protein binding rate of hydroxysafflor yellow A in safflor yellow powder injection. Chin Tradit Pat (中成药), 2011, 33(6):947-949.
[10] LI X L, CUI G N, CUI Y. Literature analysis on adverse reactions of saffower yellower injection . J China Pharm(中国药房), 2015, 26(6):732-734.
[11] ZHAO M,YANG J, WEI M J. Using confidence interval method to assess linear pharmacokinetics in dose escalation study. Chin J Clin Pharmacol(中国临床药理学杂志), 2015, 31(3):238-240.
[12] NICOLAU G, FEIGHNER J P, STOUT R, et al. Comparison of systemic exposure to nemifitide following two METHODS of subcutaneous administration to healthy volunteers. Biopharm Drug Dispos, 2005, 26(9):379-385.
[13] FORGUE S T, PATTERSON B E, BEDDING A W, et al. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol, 2006, 61(3):280-288.
[14] Ch.P (2015). VolⅡ (中国药典2015年版. 四部) [S]. 2015:360.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
重庆市科委资助项目(cstc2017shmsA130028)
{{custom_fund}}
PDF(1322 KB)
