药理效应法测定青风藤碱透皮贴剂的药动学参数  

Determination of Pharmacokinetic Parameters of Sinoacutine Transdermal Patch by Pharmacological Effect Method

作　　者：范晓 陈怡莹 姜婕 查丽春 郝佳旭 马云淑 FAN Xiaoo;CHEN Yiying;JIANG Jie;ZHA Lichun;HAO Jiaxu;MA Yunshu(School of Chinese Materia Medica,Yunnan University of Chinese Medicine,Kunming 650500 Yunnan,China;The Key Laboratory of External Drug Delivery System and Preparation Technology in University of Yunnan Province,Kunming 650500 Yunnan,China;Yunnan Key Laboratory of Dai and Yi Medicines,Kunming 650500 Yunnan,China;Yunnan Key Laboratory of Southern Medicinal Resource,Yunnan University of Chinese Medicine,Kunming 650500 Yunnan,China)

机构地区：[1]云南中医药大学中药学院,云南昆明650500 [2]云南省高校外用给药系统与制剂技术研究重点实验室,云南昆明650500 [3]云南省傣医药与彝医药重点实验室,云南昆明650500 [4]云南省南药可持续利用重点实验室,云南昆明650500

出　　处：《中药新药与临床药理》2023年第3期391-395,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81673682,82060723);云南省教育厅科学研究基金项目(2022Y360)。

摘　　要：目的利用药理效应法考察青风藤碱透皮贴剂的药动学特征,为青风藤碱透皮贴剂的临床应用提供实验依据。方法以热板法镇痛效应为评价指标,于不同时间点测定青风藤碱透皮贴剂对小鼠的痛阈净升率,考察量效关系并绘制体存量-时间曲线,计算青风藤碱透皮贴剂在小鼠体内的药动学参数;采用佐剂型关节炎大鼠模型,以大鼠肿瘤坏死因子α(TNF-α)抑制率为评价指标,用ELISA法测定不同时间点TNF-α的含量,考察量效关系并绘制体存量-时间曲线,计算青风藤碱透皮贴剂在大鼠体内的药动学参数。结果青风藤碱透皮贴剂在小鼠和大鼠体内的主要药动学参数:AUC_(0-t)分别为(2721.114±620.672)、(4158.542±89.465)mg·h·kg^(-1);AUC_(0-∞)分别为(2968.194±534.247)、(7088.899±2173.940)mg·h·kg^(-1);t_(max)均为9 h;C_(max)分别为(247.604±129.485)、(179.091±7.503)mg·kg^(-1);MRT_(0-t)分别为(10.776±0.408)、(21.424±0.804)h;MRT_(0-∞)分别为(12.855±2.870)、(53.798±24.543)h;t1/2z分别为(14.219±2.660)、(35.531±17.760)h;CLz/F分别为(0.104±0.019)、(0.045±0.012)L·h^(-1)·kg^(-1);Vz/F分别为(0.785±0.442)、(2.078±0.451)L·kg^(-1)。结论青风藤碱透皮贴剂在小鼠和大鼠体内的药动学行为呈非房室模型,在给药剂量范围内呈线性动力学特征;青风藤碱透皮贴剂达峰时间较长、达峰浓度较高,能持续控制青风藤碱在体内的释放速率,从而延长作用效果。Objective To investigate pharmacokinetic characteristics of sinoacutine transdermal patch by pharmacological effect method,and to provide an experimental basis for the clinical application of sinoacutine transdermal patch.Methods Using the analgesic effect in the hot-plate test as indicator,we calculated the net rise rates of pain threshold at different time points,obtained the dose-effect relationship and draw systemic cumulationtime curve.The pharmacokinetic parameters of sinoacutine transdermal patch in mice were computed.A model of adjuvant arthritis rats was used,and TNF-α inhibition rate was investigated,the content of TNF-α was determined by ELISA method at different time points to obtain the dose-effect relationship.Then,systemic cumulation-time curve was drawn,and the pharmacokinetic parameters of sinoacutine transdermal patch in rats was computed.Results The main pharmacokinetic parameters of sinoacutine transdermal patch in mice and rats were as following:AUC_(0-t)=(2 721.114±620.672),(4 158.542±89.465)mg·h·kg^(-1);AUC_(0-∞)=(2 968.194±534.247),(7 088.899±2 173.940)mg·h·kg^(-1);t_(max)=9 h;C_(max)=(247.604±129.485),(179.091±7.503)mg·kg^(-1);MRT_(0-t)=(10.776±0.408),(21.424±0.804)h;MRT_(0-∞)=(12.855±2.870),(53.798±24.543)h;t_(1/2z)=(14.219±2.660),(35.531±17.760)h;CL_z/F=(0.104±0.019),(0.045±0.012)L·h^(-1)·kg^(-1);V_z/F=(0.785±0.442),(2.078±0.451)L·kg^(-1).Conclusion The pharmacokinetic process of sinoacutine turbodermal patch is in line with non-compartment model in mice and rats.Linear dynamics feature was observed in the range of administered doses.Sinoacutine turbodermal patch showed a longer arrived peak time and higher peak concentration,which can continuously control the release rate of sinoacutine and thereby prolong the effect.

关 键 词：青风藤碱 透皮贴剂 药理效应法 药物动力学 小鼠 大鼠 

分 类 号：R285.5[医药卫生—中药学]