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. Twocompartment model the twocompartment model resolves the body into a central compartment and a peripheral compartment see figure 1. The rate of a process is the change in velocity or speed with in relation to time. 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. 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. The initial twostage analysis comparing one, two, and three compartmental models found that the two compartmental model shows the best fit to the experimental data.
Pdf compartmental models are composed of sets of interconnected mixing. There is an additionnal parameter to estimate, k e0 the equilibrium rate constant between central and e ect compartment. 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 best and the simplest way of estimating vd of a drug is administering it by rapid i. Compartment is the traditional and most widely used approach to pharmacokinetic characterization of drug. Kinetics is the study of the rate of a process and the factors affecting on it. More complicated physiologicallybased models combine many simple models. 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. On the volume of distribution at steady state and its relationship with two compartmental models james w. 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. Phar 7633 chapter 19 multicompartment pharmacokinetic models. Multi compartment characteristics are best described by administration as i. 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.
Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. 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. The theoretical biology analysis, uses mathematical and physical models and bioinformatics tools in practical medicine. Noncompartmental model is often estimated by auc and other parameters, like c max, c min, and t max. Godfrey department ofengineering, university of warwick, coventry cv4 7al, uk abstract. In this first exercise we shall study a simple one compartment one reservoir pharmacokinetic model. Pharmacokinetics model is the central piece of model based drug development.
Arundel drug metabolism and pharmacokinetics, astrazeneca, alderley park, cheshire sk10 4tg, united kingdom. Pharmacokinetics from ancient greek pharmakon drug and kinetikos moving, putting in motion. The concentration of drug in the body is determined not only by the rate constant values but also by the apparent volume of distribution. Noncompart provides basic computational functions for nca. They are a convenient oversimplification used to predict the concentration of a drug at any given time in any given body fluid or tissue. For each model the equation for c et is given after the corresponding one for ct. This result was also confirmed by a population analysis. In pharmacokinetics the concentrationtime profiles of many drugs can be approximated using compartmental models. Model independent method overcomes some of the drawbacks associated with classical compartment modeling. A two compartment model is a satisfactory oversimplification to. 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.
This model represents the simplest way to describe the process of drug. Concentration is measured in compartment 1 in both cases. Modeling of pharmacokinetics and pharmacodynamics with. Pdf compartmental modeling in the analysis of biological. A threecompartment pharmacokinetic model to predict the. Pharmacokinetics was defined as 12 of pharmacology. The sketch diagram of the pharmacokinetic model is given in fig. Explain using examples why drugs follow one compartment, two compartment, or three compartment kinetics. Pdf a multicompartment pharmacokinetic model of the interaction. Pharmacokinetics to compartmental models poggesi et al. 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 pk, compartmental models are in widespread use for. 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. The analysis in silico reduces time and costs of new designed drugs and provides wider spectrum of information for exploration. There is an additionnal parameter to estimate, k e0 the equilibrium rate constant between central and e.
Usually, pharmacokinetics study involves considering both experimental and theoretical approaches. Linear timeinvariant compartmental models nonlinear compartmental models compartmental modelling. Introduction to pharmacokinetics and pharmacodynamics. The movement of a drug within the body is described by the following process. The compartmental models assume that the body is composed of one or more compartments into which the drug is distributed after admini. Pharmacodynamics research unit, the upjohn company, kalamazoo, ml 49001. Many may be asking why we use compartment models in pharmacokinetics. Physiologicallybased pharmacokinetics is a complex predictive tool integrating into an in. Noncompartment pharmacokinetics is a new approach devised to study the time course of drug in the body with out assuming any compartment model. View the article pdf and any associated supplements and figures for a period of 48 hours. Compartmental model a compartment is a group of tissues with similar blood flow and drug affinity. Vd is a measure of the extent of distribution of drug and is expressed in liters. In pharmacokinetics the above parameters are assumed to be constants.
A single compartment model is the least accurate, as it assumes a homogeneous distribution of the drug in the body. Compartmental systems proved to be useful models in various biological domains including physiology, pharmacokinetics, population dynamics, and epidemiology 5, 15, 18. The compartmental modeling of pharmacokinetics consists in describing the fate of a drug in the body, depicted as an entity divided into compartments. Pharmacokinetics is the science of the kinetics of drug absorption, distribution, and elimination i. 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. It is performed by noncompartmental or compartmental methods.
The substances of interest include any chemical xenobiotic such as. Performs traditional nca and simulationbased posterior predictive checks for a population pk model using nca metrics. Our focus is on a onecompartment pharmacokinetic model, specifically aimed at different. 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. It targets summarizing data from model fit or simulated sources. Pharmacokinetics of drugs following iv bolus, iv infusion, and oral.
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. What is one compartment modelling in pharmacokinetics. 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. This type of modelling is called compartment modelling. In that case a model in library pke0 appendix ii should be used. 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. Two major groups of compartmental models can be identified. Hopefully you now understand what is meant by compartmental models in pharmacokinetics. Pdf compartmental modeling in the analysis of biological systems. The simplest and commonest is the two compartment model which classifies the body tissues in two categories. Compartment models pharmacokinetics studies the movement of drugs in the body. Mathematical expressions of the pharmacokinetic and. On the volume of distribution at steady state and its.
Elimination rate constant of central compartment and tissue compartment because of redistribution of drug out of tissue compartment,b is smaller than k. Phar 7633 chapter 19 multicompartment pharmacokinetic. Pharmacodynamic models deal with the action of the drug once it reaches its target organ. Pharmacokinetics of drugs following iv bolus, iv infusion. Compartmental modeling in the analysis of biological systems article pdf available in methods in molecular biology clifton, n. These models simply interpolate the instrumental data and allow on empirical formula to. A more complex analysis of both pharmacokinetics and pharmacodynamics of remifentanil has been also approached 8. In humans and related organisms, there are five major body compartments. Pdf compartmental model of the pharmacokinetics of drugs.
A new mathematical framework is introduced for combining the linear compartmental models used in pharmacokinetics with the spatiotemporal distributions of. Pdf background in this paper the interactions between paclitaxel, doxorubicin and the metabolic enzyme cyp3a4 are studied using. Let us consider the two compartmental model depicted in fig. Impact of saturable distribution in compartmental pk models. Compartment models simulate drug absorption distribution and elimination. 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. Special consideration is given to the fact that it is impossible from a single i. Apply one compartment pharmacokinetics to single and multiple.
Although a complete model would incorporate both parts, each type is independently useful for different purposes. Pk allows estimation of pharmacokinetic parameters using non compartmental theory. 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 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. In essence, the number 1, 2, 3 refers to the number of circles drawn on the paper. The brief answer is that the mathematical functions associated with compartment models seem to describe. Pharmacodynamics research unit, the upjohn company, kalamazoo, michigan.
Different pharmacokinetic parameters in noncompartment model. Onecompartment pharmacokinetic models are considered for. Compartmental analysis is the most often used pharmacokinetic. Central compartment or compartment 1 peripheral or tissue. The peripheral compartment consists of the less perfused tissues like skin, bone, cartilages etc. Compartmental pk models usually combine a central or plasma compartment, which represents the site at which pharmacokinetic sampling.
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