摘要
房室模型和统计矩模型是药物代谢动力学的重要理论,但受药物分布的影响,有明显局限。房室模型的分布相与消除相的分界点有时难以判定,对其应用带来不便,药物按器官血流速度差异分房室的理论也值得商榷。统计矩模型的零阶矩AUC的本质是血药浓度,而不是药量;对于二室或多室模型药物,其结果反映血药浓度的变化,而不一定是体内药量的变化。缓慢恒速静脉滴注过程中,体内的药物分布基本平衡,血药浓度的变化基本反映体内药量变化。滴注超过5个半衰期,血药浓度基本达稳态,停药后血药浓度的变化仅反映药物消除。对于一级动力学消除药物,可根据消除规律(lnC=lnC0-Kt),直线回归计算出消除速率常数(K),再依次计算出消除半衰期(t1/2)、稳态时体内药物量(Ass)、表观分布容积(Vd)和清除率(CL)。缓慢恒速静脉滴注过程中,体内药量和血药浓度呈正比,血药浓度(Ct)与时间(t)呈指数关系[Ct=C0+(Css-C0)×(1-e^-Kt)]。将Ct与t进行一阶指数回归,可计算出消除阈浓度(C0)、稳态血药浓度(Css)和K,再依次计算出t1/2、Ass、Vd和CL。这种分布平衡模型避免了药物分布的干扰,更接近实际。
Compartment model and statistical moment model are important theories of pharmacokinetics.However, they have obvious limitations due to the influence of drug distribution.Sometimes, the demarcation point between the distribution phase and the elimination phase of the compartment model is difficult to determine, which results in inconvenience for its application.The nature of zero order moment, AUC of statistical moment model, is blood drug concentration, but not drug amount in the body.For drugs of two-compartment or multi-compartment models,the results reflect alterations in blood drug concentration, not necessarily changes in the amount of drug in the body.In the slow and steady intravenous drip, the drug distribution in the body is basically balanced, and the alteration of blood drug concentration can reflect the alteration of drug amount in the body.Over 5 half-life, the blood drug concentration basically reaches a stable status.And the alteration of the blood drug concentration only reflects the drug elimination.For first-order kinetic drugs, the elimination rate constant ( K ) can be calculated by linear regression according to the elimination rule ( ln C= ln C 0-K t).And then, the half-life ( t 1/2 ), the amount of drug in the body, the apparent distribution volume ( Vd ), and the clearance rate ( CL ) can be calculated successively.During slow and constant velocity intravenous dripping, drug amount is proportional to blood drug concentration in the body.And there is an exponential relationship between the blood drug concentration and time [ C t = C 0 +( C ss - C 0 )(1-e^-Kt )].The first-order exponential regression is performed between C t and t to calculate elimination threshold concentration ( C 0), steady blood drug concentration ( C ss ) and K .Then, t 1/2 , steady drug amount ( A ss ), Vd and CL are calculated.The distributed equilibrium model avoids the interference of drug distribution, and is closer to reality.
作者
曹永孝
CAO Yong-xiao(Department of Pharmacology, Xi an Jiaotong UniversityHealth Science Center, Xi an 710061, China)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2019年第5期669-673,共5页
Journal of Xi’an Jiaotong University（Medical Sciences）
关键词
药物代谢动力学
房室模型
统计矩模型
药物分布平衡
pharmacokinetics
compartment model
statistical moment model
drug distribution equilibrium
作者简介
通信作者:曹永孝,西安交通大学药理学教授,博士,博士生导师。国家医学考试专家委员会委员,国家自然科学基金评审专家,新药审评专家。西安交通大学教学名师,Toxicology&Applied Pharmacology副主编,United Journal of Pharmacology and Threapeutics、西安交通大学学报(医学版)、海峡药学等编委。中国药理学会药理教学专业委员会常务委员,陕西省老年学和老年医学会药学专业委员会主任委员。主编国家规划教材2部,副主编5部。主持和参与国家、省部级科研基金20项。发表论文280篇,其中SCI收录80篇,申请发明专利20项,主持药理毒理研究60余项,制定陕西省保健用品评价标准9项。培养硕士、博士生50余名,获王宽诚育才奖、中国高等教育学会高校教学改革优秀案例奖。指导大学生获全国大学生创新竞赛一等奖2项,省级一等奖2项。E-mail:yxy@xjtu.edu.cn.
