If a known set of drug concentrations in the body is determined at various time intervals then the volume of the body fluid and the rate of drug elimination is established. In that case a model in library pke0 appendix ii should be used. The movement of a drug within the body is described by the following process. Compartmental analysis is the most often used pharmacokinetic. Noncompartmental model is often estimated by auc and other parameters, like c max, c min, and t max. Pharmacokinetics was defined as 12 of pharmacology. Compartment models simulate drug absorption distribution and elimination. Phar 7633 chapter 19 multicompartment pharmacokinetic. Although these compartments have no physiological or anatomical meaning, it is assumed that the central compartment comprises tissues that are highly perfused such as heart, lungs, kidneys.
In pharmacokinetics the concentrationtime profiles of many drugs can be approximated using compartmental models. Usually, pharmacokinetics study involves considering both experimental and theoretical approaches. There is an additionnal parameter to estimate, k e0 the equilibrium rate constant between central and e. Pk allows estimation of pharmacokinetic parameters using non compartmental theory. The best and the simplest way of estimating vd of a drug is administering it by rapid i. The substances of interest include any chemical xenobiotic such as. A new mathematical framework is introduced for combining the linear compartmental models used in pharmacokinetics with the spatiotemporal distributions of. Pdf compartmental modeling in the analysis of biological systems.
Detailed mathematical modeling of several pharmacokinetics studies are given by gabrielsson and weiner 2006, and a few basic concepts from this reference are discussed in this section. For each model the equation for c et is given after the corresponding one for ct. An experiment has been carried out in man designed to compare the fit of a two and a three compartment pharmacokinetic model to experimentally determined serum digoxin concentrationtime data following rapid intravenous injection of 1. Compartmental pk models usually combine a central or plasma compartment, which represents the site at which pharmacokinetic sampling. Noncompart provides basic computational functions for nca. After an introduction in which terns commonly used in the pharmacokinetics literature are defined, the role of linear, timeinvariant compartrrental models in pharmacokinetics is discussed. Central compartment or compartment 1 peripheral or tissue. Assume that q i t v i c t, for i 1, 2 denote the amount of a drug in a specific compartment. In pharmacokinetics the above parameters are assumed to be constants. The concentration of drug in the body is determined not only by the rate constant values but also by the apparent volume of distribution. Compartmental model the compartment concept is utilized in pharmacokinetics when it is necessary to describe the plasma concentration versus time data adequately and accurately to obtain accurate estimates of selected fundamental pharmacokinetics parameters such as the apparent volume of drug distribution, the elimination half life and the elimination rate constant of a drug. The theoretical biology analysis, uses mathematical and physical models and bioinformatics tools in practical medicine. The simplest and commonest is the two compartment model which classifies the body tissues in two categories.
Explain using examples why drugs follow one compartment, two compartment, or three compartment kinetics. In pharmacokinetics pk, compartmental models are in widespread use for. Physiologicallybased pharmacokinetics is a complex predictive tool integrating into an in. Compartment models pharmacokinetics studies the movement of drugs in the body. More complicated physiologicallybased models combine many simple models. A single compartment model is the least accurate, as it assumes a homogeneous distribution of the drug in the body. These models simply interpolate the instrumental data and allow on empirical formula to. Multicompartmentaltwo compartment body model 1 two compartment body model and vd terms by jeff stark in a one compartment model, we make two important assumptions. The brief answer is that the mathematical functions associated with compartment models seem to describe. Introduction to pharmacokinetics and pharmacodynamics. In essence, the number 1, 2, 3 refers to the number of circles drawn on the paper. Although a complete model would incorporate both parts, each type is independently useful for different purposes. Arundel drug metabolism and pharmacokinetics, astrazeneca, alderley park, cheshire sk10 4tg, united kingdom. Phar 7633 chapter 19 multicompartment pharmacokinetic models.
This result was also confirmed by a population analysis. Kinetics is the study of the rate of a process and the factors affecting on it. Pharmacokinetics is the science of the kinetics of drug absorption, distribution, and elimination i. Onecompartment pharmacokinetic models are considered for. Pdf compartmental modeling in the analysis of biological. Impact of saturable distribution in compartmental pk models. Elimination rate constant of central compartment and tissue compartment because of redistribution of drug out of tissue compartment,b is smaller than k. Compartmental model the compartment concept is utilized in pharmacokinetics when it is necessary to describe the plasma concentration versus time data adequately and accurately to obtain accurate estimates of selected fundamental pharmacokinetics parameters such as the apparent volume of drug distribution, the elimination half life and the. On the volume of distribution at steady state and its relationship with two compartmental models james w. Norman pharmacokinetics may appear daunting, especially if the background mathematical development is presented too briefly and if the number of compartments or subdivisions of the model are too many.
The sketch diagram of the pharmacokinetic model is given in fig. Here c t is the concentration of a drug and v t is the volume of the i th compartment and k ij is the fractional rate of transfer to compartment i from compartment j. A two compartment model is a satisfactory oversimplification to. Pdf background in this paper the interactions between paclitaxel, doxorubicin and the metabolic enzyme cyp3a4 are studied using. Pharmacokinetics model is the central piece of model based drug development.
Half life clearance zero and first order kinetics volume of distribution bioavailability area under the plasma concentration timecurve extraction ratio b to describe absorption and factors that will influence it with reference to clinically. In this first exercise we shall study a simple one compartment one reservoir pharmacokinetic model. Compartment is the traditional and most widely used approach to pharmacokinetic characterization of drug. Pdf compartmental model of the pharmacokinetics of drugs. Multi compartment characteristics are best described by administration as i. Apply one compartment pharmacokinetics to single and multiple. The rate of a process is the change in velocity or speed with in relation to time. Performs traditional nca and simulationbased posterior predictive checks for a population pk model using nca metrics.
Many may be asking why we use compartment models in pharmacokinetics. It targets summarizing data from model fit or simulated sources. Pharmacokinetics to compartmental models poggesi et al. Compartmental model a compartment is a group of tissues with similar blood flow and drug affinity. Use equations and graph to simulate plasma drug concentration at various time periods after an iv bolus injection of a drug that follows the pharmacokinetics of a two and three compartment model. It is performed by noncompartmental or compartmental methods. Modeling of pharmacokinetics and pharmacodynamics with. Compartmental systems proved to be useful models in various biological domains including physiology, pharmacokinetics, population dynamics, and epidemiology 5, 15, 18. There is an additionnal parameter to estimate, k e0 the equilibrium rate constant between central and e ect compartment. The peripheral compartment consists of the less perfused tissues like skin, bone, cartilages etc. 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. The compartmental modeling of pharmacokinetics consists in describing the fate of a drug in the body, depicted as an entity divided into compartments. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Linear timeinvariant compartmental models nonlinear compartmental models compartmental modelling.
This type of modelling is called compartment modelling. This model represents the simplest way to describe the process of drug. Godfrey department ofengineering, university of warwick, coventry cv4 7al, uk abstract. Digoxin was administered to five healthy male volunteers, blood samples were withdrawn repetitively over a period of 72 hr, and. Two major groups of compartmental models can be identified. Pharmacodynamics research unit, the upjohn company, kalamazoo, ml 49001.
Hopefully you now understand what is meant by compartmental models in pharmacokinetics. Compartmental modeling in the analysis of biological systems article pdf available in methods in molecular biology clifton, n. Vd is a measure of the extent of distribution of drug and is expressed in liters. What is one compartment modelling in pharmacokinetics. They are a convenient oversimplification used to predict the concentration of a drug at any given time in any given body fluid or tissue. Pharmacokinetics of drugs following iv bolus, iv infusion, and oral. Our focus is on a onecompartment pharmacokinetic model, specifically aimed at different.
Pharmacokinetics of drugs following iv bolus, iv infusion. The onecompartment open model is the simplest model which depicts the body as a single, kinetically homogenous unit that has no barriers to the movement of drug and final distribution equilibrium between the drug the plasma and other body fluids is attained instantaneously and maintained at all times. The drug leaves the site of administration absorption to enter a central compartment, from which it is both exchanged with peripheral compartments distribution and irreversibly eliminated. Different pharmacokinetic parameters in noncompartment model. In humans and related organisms, there are five major body compartments. 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. Twocompartment model the twocompartment model resolves the body into a central compartment and a peripheral compartment see figure 1. Phar 7633 chapter 19 multi compartment pharmacokinetic models effect of k12 and k21 on drug concentration versus time changing the ratio of k12 to k21 figure 19. Various multicompartment models can be used in the areas of pharmacokinetics and pharmacology, in the support of efforts in drug discovery, and in environmental science. On the volume of distribution at steady state and its. The analysis in silico reduces time and costs of new designed drugs and provides wider spectrum of information for exploration. Pharmacodynamic models deal with the action of the drug once it reaches its target organ. View the article pdf and any associated supplements and figures for a period of 48 hours. Pdf a multicompartment pharmacokinetic model of the interaction.