Population Pharmacokinetic/Pharmacodynamics Modeling and Safety/Tolerability Assessing of Qishe Pill in 2 Major Constitutional Types of Healthy Chinese Subjects: Study Protocol for a PhaseⅠClinical Trial
Purpose:To assess pharmacokinetics,pharmacodynamics,tolerability and safety of oral medication of Qishe Pill in healthy Chinese subjects.To describe the population pharmacokinetic profile of Qishe Pill and to compare its extent of metabolism in 2major Constitution Type (Qi-Deficiency and Blood Stasis) of each 12 healthy Chinese subjects.Methods/design:The study will take place at the Phase Ⅰ Unit of Longhua Hospital,Shanghai University of TCM in Shanghai from September 2014 to December 2014.Firstly,24 subjects will be equally divided into 3 groups (3.75g;7.5g;15g).For single-dose stage,samples will be collected at dosing (time 0) and at 15,30,45,60,90,120,150,180,240,360,480,600,720,1440,2160 and 2880 min after dosing.For the PK analysis,5 ml blood samples will be collected.The Pharmacokinetic Parameters assessed include area under the plasma concentration-time curve (A UCo-tn,A UCo-∞),maximum plasma concentration (Cmax),terminal half-life (t1/2),clearance (CL),apparent volume of distribution during the terminal phase (Vz),and mean residence time (MRT).Pharmacodynamic analyses include the determination of ACT,PT and APTT.Safety and tolerability will be assessed subjectively and objectively.16 subjects will be equally divided into 2 groups (7.5g,per 24 hour for 6days;or 3.75g,per 12 hour for 6 days).For multiple-dose stage,Samples will be collected at 15,30,45,60,90,120,150,180,240,360,480,600,720,1440,2160and 2880 min after the 6th day dosing.Subjective tolerability will be assessed by questioning subjects about any adverse events (AE).Objective tolerability will be assessed at scheduled intervals by physical examination,safety laboratory tests,vital sign measurements (blood pressure and pulse rate,body temperature),electrocardiogram (ECG) recordings and fecal occult blood testing (FOBT).Discussion: Qishe Pill is composed of processed Radix Astragali,Muscone,Szechuan Lovage Rhizome,Radix Stephaniae Tetrandrae,Ovientvine,and Calculus Bovis Artifactus.Over last several years,several interactions have been reported in literature describing the interference of Qishe pill on the pharmacokinetics.In the pilot trial of limited size,a UPLC-TQ/MS method for simultaneous determination of plasma concentrations of 15 bio-active constituents of Qishe pill was developed and validated.The results showed that the method was selective,sensitive,precise,accurate,and reliable for comparative quantification.Moreover,traditional Chinese constitutional types in traditional Chinese recipe could significantly influence the blood drug concentration and their pharmacokinetic parameters after oral administration.If the difference in the pharmacokinetics of Qishe pill between the two major constitutional group have been detected,some personal medication strategies for people with the 2 major constitutional types will be provided for the scope of application of TCM.
Cervical radiculopathy Neck pain Qishe pill Traditional Chinese medicine healthy Chinese subject Pharmacokinetics Pharmacodynamics Tolerability
Yue-li Sun Ting Hou Shu-fen Liu Zhong-liang Zhang Ning Zhang Min Yao Long Yang Qi Shi Xue-jun Cui Yong-jun Wang
Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,ER.China;Spine College of Traditional Chinese Herbal Medicine,Shanghai University of Traditional Chinese Medicine,S Zhe Jiang Biosia Pharmaceutical Co.,Ltd,Shanghai,201203,P.R.China
国内会议
世界中联伦理审查委员会第四届学术年会暨世界中联临床疗效评价专业委员会第八届学术年会
沈阳
英文
376-386
2014-05-27（万方平台首次上网日期，不代表论文的发表时间）