One compartment model pharmacokinetics pdf

This model assumes that the drug can enter or leave the body ie, the model is open, and the entire body acts like a single, uniform compartment. Clinical pharmacokinetics is a practical guide to the use of pharmacokinetic principles in clinical practice. Intravenous bolus administration onecompartment open model the simplest route of drug administration from a modeling perspective is a rapid intravenous injection iv bolus. The pharmacokinetics have been described using a onecompartment intravenous infusion model. What is one compartment modelling in pharmacokinetics. View the article pdf and any associated supplements and figures for a period of 48 hours. A statistical evaluation of the goodness of the models has been carried out following the akaike information criterion 9. Noncompartment pharmacokinetics is a new approach devised to study the time course of drug in the body with out assuming any compartment model.

The sketch diagram of the pharmacokinetic model is given in fig. A log scale plot of the serum level decay curve of a 1compartment model yields a straight line. It presumes that a drugs bloodplasma concentration is a true reflection of the concentration in other tissues and that the elimination of the drug is directly proportional to the drugs concentration in the organism. Central compartment the central compartment includes the wellperfused organs and tissues heart, blood, liver, brain and kidney with which drug equilibrates rapidly. The one compartment pharmacokinetic model can be represented schematically as. It assumes that the drug is administered instantly into the body, it is instantaneously and rapidly distributed throughout the body, and drug elimination occurs immediately upon entering the body. Model independent method overcomes some of the drawbacks associated with classical compartment modeling. One compartment open model is presented in an elaborate manner to make the students familiar with various aspects of pharmacokinetics mathematical equations are developed using simple integration and differentiation methods practice problems are provided wherever necessary, and a question bank is included at the end of each chapter.

Over 30 clinical cases with selfstudy questions and answers are presented throughout to bridge the gap between pharmacokinetic concepts and. Depending on rate of input, several one compartment open models are. Pharmacokinetics can be reduced to mathematical equations, which describe the transit of the drug throughout the body, a net balance sheet from absorption and distribution. One compartment model pharmacokinetics pdf understand the properties of first order kinetics, linear models be able to write the differential equations for a simple pharmacokinetic model. We begin with the simplest case, infusion of the biologically inert substance, inulin. Compartmental model a compartment is a group of tissues with similar blood flow and drug affinity. Pharmacokinetics of drugs following iv bolus, iv infusion, and oral. Basic assumption is that drug or metabolite follows. A onecompartment model may be used for drugs which rapidly equilibrate with the tissue compartment, e. Introduction to pharmacokinetics and pharmacodynamics ashp. Bolus objectives understand the assumptions used for this model understand the properties of first order processes linear processes use appropriate integrated equations use and calculate the parameters. We consider these cases to illustrate the effectiveness of the nsfd method for the solution of nonlinear differential equations of this nature. There is an additionnal parameter to estimate, k e0 the equilibrium rate constant between central and e ect compartment.

Clinical correlate drugs that have extensive distribution outside of plasma appear to have a large volume of distribution. Kinetics is the study of the rate of a process and the factors affecting on it. Introduction to pharmacokinetics and pharmacodynamics. A pharmacokinetic model is a model devised to simulate the rate process of drug absorption.

For each model the equation for cet is given after the corresponding one for ct. In many ways the compartmental models are very similar to the heart chamber model. Onecompartment pharmacokinetic models are considered for different routes of administration. For example, for the onecompartment model with an intravenous bolus dose administration, the rate at which the drug moves in the central compartment can be calculated by the following differential equation, da 1. A single compartment simulation model of pharmacokinetics. There are two parameterisations implemented in pfim for onecompartment models, v and k or v and cl. For drugs to be effective they need to be able to move rapidly from blood plasma to other body fluids. Today, increased physiologic understanding of pharmacokinetics shows that halflife is a secondary parameter that depends upon the primary parameters clearance and apprent volume. Phar 7633 chapter 8 pharmacokinetics of oral administration scheme or diagram this model can be represented as. Represent graphically the typical natural log of plasma drug concentration versus time curve for a one compartment model after an intravenous dose. These models simply interpolate the instrumental data and allow on empirical formula to. History of pharmacokinetics 539 pharmacokinetic models. In one compartment model, the body is treated as a single compartment to which drug is added. This metaanalysis was performed with a multivariate nonlinear mixed model.

Thus, the one compartment open model with iv bolus administration is the simplest pharmacokinetic model. Pharmacokinetics of drugs following iv bolus, iv infusion. Noncompartmental model thinks of an organism as only one homogenous compartment. Usually, pharmacokinetics study involves considering both experimental and theoretical. The peripheral compartment consists of the less perfused tissues like skin, bone, cartilages etc. Biopharmaceutics and pharmacokinetics download ebook pdf. Contents of the powerpoint on non compartmental pharmacokinetics include. Injection only urinary elimination a 70 kg patient was given a bolus i. Pharmacodynamics research unit, the upjohn company, kalamazoo, michigan. The following figure compares a model as typically represented in pharmacokinetics with the same model shown in the simbiology model diagram. The onecompartment model implemented in pfim is described in figure 1. The onecompartment open model assumes that the body can be described as a single, uniform compartment ie, one compartment, and that drugs can enter and leave the body ie, open model. One compartment open model i v infusion authorstream.

Examples include digoxin, diltiazem, imipramine, labetalol, metoprolol, meperidine, and nortriptyline. The library of pharmacokinetic pk and pharmacodynamic pd models. All the symbols imply is that, for a set of values of a dependent variable, there is some. Introduction to pharmacokinetics and pharmacodynamics pharmacokinetics. Mathematical expressions of the pharmacokinetic and pfim. The onecompartment open model offers the simplest way to describe the process of drug distribution and elimination in the body. When the plasma concentration c p was assayed, the following data was obtained. Pharmacokinetics model is the central piece of model based drug development. It comprised a fivecompartment scheme representing the cir culatory system, a drug depot, fluid volume, kidney elimination and tissue inactivation. One compartment pharmacokinetics biological background inulin is an inert polysaccharide that is infused into animals or humans to estimate the volume of. Pharmacokinetic onecompartment model pharmacokinetics refers to the rate and extent of distribution of a drug to different tissues, and the rate of elimination of the drug. Can be known by actual measurement or estimated by using cp0 f dvd. The simplest drug administration is when the entire drug is given in a rapid iv injection, also known as an iv bolus. A compartment in pharmacokinetics is an entity that can be described by a definite volume and a concentration of a drug contained in that volume, which may be.

Peripheral compartments the peripheral compartments includes those organs e. The concentration profile could be best described using a twocompartment model with firstorder absorption and elimination. There are two parameterisations implemented in pfim for one compartment models, v and k or v and cl. The simplest route of drug administration from a modeling. The one compartment model and bioavailability flashcards.

These models show movement from one chamber to another. Mathematical expressions of the pharmacokinetic and. Modeling of pharmacokinetics and pharmacodynamics with. A pharmacokinetic model is a model devised to simulate the rate process. Cpt concentration in plasma at defined time interval after the time of known concentration corresponding to a a known or estimated concentration. The compartmental models assume that the body is composed of one or more compartments into which the drug is distributed after admini.

Phar 7633 chapter 8 pharmacokinetics of oral administration. This paper proposed an important approach to transform published noncompartment model pharmacokinetics pk parameters into compartment model pk parameters. Pdf pharmacokinetics of drugs following iv bolus, iv. For a drug that follows one compartment kinetics and administered. In that case a model in library pke0 appendix ii should be used. Moreover, the pharmacodynamics have been fitted using inhibitory model. A twocompartment model should be used for drugs which slowly equilibrate with the tissue compartment, e. A mammillary model with one compartment, parameterized in microconstant vand ka or with cland v b. One compartment open model, extravascular administration, firstorder absorption. The drug is not bound to plasma proteins and is excreted unchanged solely into the urine. The onecompartment open model is the simplest way to describe the process of drug distribution and elimination in the body. The rate of a process is the change in velocity or speed with in relation to time. The 2compartment model considers the entire body, and all of the organs and tissues to be two buckets, but all drug must leave the body through a single bucket.

The onecompartment open model is the simplest model which depicts the body as a single. For each model the equation for c et is given after the corresponding one for ct. Apply onecompartment pharmacokinetics to single and multiple. In pharmacokinetics the concentrationtime profiles of many drugs can be approximated using compartmental models. Pdf pharmacokinetics of drugs following iv bolus, iv infusion. Describe the distribution of drug in the body once administered one compartment model. For this comparison, assume that you are modeling administration of a drug using a twocompartment model with any dosing input and linear elimination kinetics.

The brain and bones as well as other parts of the central nervous system is excluded, since most drugs have little penetration into these organs. Linear pharmacokinetics is socalled because the graph of the relationship between the various factors involved dose, blood plasma concentrations, elimination, etc. Compartment is the traditional and most widely used approach to pharmacokinetic characterization of drug. Represent graphically the typical natural log of plasma drug concentration versus time curve for a onecompartment model after an intravenous dose.

Introduction to noncompartmental pharmacokinetic approach differences between compartment and noncompartment models concepts of noncompartmental model statistical moments theorymean residence time different pharmacokinetic parameters in noncompartment model. Drug exhibits the characteristics of one compartment model. Pharmacokinetics is the science of the kinetics of drug absorption, distribution, and elimination i. Pharm11b2 what is meant by the term two compartment. Cpt a e ke t mgl mgl e frcnhr hr using a calculator.