A method to determine pharmacokinetic parameters based on andante constant-rate intravenous infusion. 2017

Rui-Hong Yu, and Yong-Xiao Cao
Department of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, China.

On account of the disturbance from the distribution phase, the concentration-time curve of drugs cannot fully reflect the characteristics of elimination, and thus, it is difficult for present methods to obtain ideal pharmacokinetic parameters. This paper presents a method to determine pharmacokinetic parameters based on an andante constant-rate intravenous infusion. A mathematical model of the constant-rate intravenous infusion combined with the elimination of first-order kinetics was established. During infusion, the accumulation tendency of drugs was deduced as [Formula: see text] using the principle of calculus. Then, the method to determine the pharmacokinetic parameters was summed up. After collecting the blood drug concentration (C t ) -time (t) data from a constant-rate (v) infusion period, an exponential regression analysis was conducted to obtain the elimination rate constant (K) and plateau concentration (C ss ). Then, the half-life (t 1/2 ), apparent volume of distribution (V d ) and clearance rate (CL) were calculated based on the equations, t 1/2  = 0.693/K, V d  = (v/K)/C ss and CL = v/C ss , respectively. In addition, an application example of cimetidine in a beagle dog was used to demonstrate the implementation process of the method.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008962 Models, Theoretical Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Experimental Model,Experimental Models,Mathematical Model,Model, Experimental,Models (Theoretical),Models, Experimental,Models, Theoretic,Theoretical Study,Mathematical Models,Model (Theoretical),Model, Mathematical,Model, Theoretical,Models, Mathematical,Studies, Theoretical,Study, Theoretical,Theoretical Model,Theoretical Models,Theoretical Studies
D002927 Cimetidine A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output. Altramet,Biomet,Biomet400,Cimetidine HCl,Cimetidine Hydrochloride,Eureceptor,Histodil,N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine,SK&F-92334,SKF-92334,Tagamet,HCl, Cimetidine,Hydrochloride, Cimetidine,SK&F 92334,SK&F92334,SKF 92334,SKF92334
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions

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