Pdf pharmacokinetics of drugs following iv bolus, iv infusion. Jan 22, 2014 contents of the powerpoint on non compartmental pharmacokinetics include. Pharmacokinetics getting to the target pharmacodynamics action at the target now look at pharmacokinetics in a more practical, quantitative sense. Noncompartment model to compartment model pharmacokinetics. Thus, the one compartment open model with iv bolus administration is the simplest pharmacokinetic model.
Noncompartmental model is often estimated by auc and other parameters, like c max, c min, and t max. May 28, 2010 pharmacokinetics model is the central piece of model based drug development. Noncompartment pharmacokinetics is a new approach devised to study the time course of drug in the body with out assuming any compartment model. Introduction to pharmacokinetics and pharmacodynamics ashp. Mammillary model this is the most common compartment used in pharmacokinetics. The one compartment model assumes that any change in the plasma levels of drug reflects proportional changes in tissues drug concentrations. The concentration profile could be best described using a twocompartment model with firstorder absorption and elimination. Multicompartment models explain the observation that, after a rapid iv bolus drug injection, the plasma leveltime curve does not decline linearly, implying that the drug does not equilibrate rapidly in the body, as observed for a single firstorder rate process in a onecompartment model. Pharmacokinetics from ancient greek pharmakon drug and kinetikos moving, putting in motion. Pharmacokinetics and pharmacodynamics onecompartment model for theophylline. For many drugs, a onecompartment model can adequately describe the pk and guide drug dosing, but for most drugs used in anaesthesia this is not the case.
Introduction to pharmacokinetic models biopharmaceutics and pharmacokinetics. For three compartment model equations, ct c 1t represent the drug concentration in the rst compartment, c 2t represents the drug concentration in the second compartment, and c 3t represents the drug concentration in the third compartment. Phar 7633 chapter 19 multi compartment pharmacokinetic models student objectives for this chapter to draw the scheme and write the differential equations appropriate to a multi compartment pharmacokinetic model to recognize and use the integrated equations for these models to calculate parameter values and for dosage regimen calculations. Contents of the powerpoint on non compartmental pharmacokinetics include. Pharmacokinetics getting to the target pharmacodynamics action at the target. Multicompartmentaltwo compartment body model 1 two compartment body model and vd terms by jeff stark in a onecompartment model, we make two important assumptions. Jul 18, 2018 for many drugs, a one compartment model can adequately describe the pk and guide drug dosing, but for most drugs used in anaesthesia this is not the case. Three examples of nonlinear models are then discussed. Clinical pharmacokinetics and pharmacodynamics of propofol.
These models show movement from one chamber to another. The three compartment model implemented in pfim is described in figure 1. Modeling the pharmacokinetics and pharmacodynamics of. Model for drug administered via an extravascular route f bioavailability fraction d dose administered c, t. Clinical correlate digoxin, particularly when given intravenously, is an example of a drug that is well described by twocompartment pharmacokinetics. Clinical pharmacokinetics is a practical guide to the use of pharmacokinetic principles in clinical practice. Introduction to pharmacokinetics and pharmacodynamics. Zeroorder rate drug administration and firstorder rate drug elimination. For example, in a twocompartment model, tissues, into which the drug distributes more slowly, are lumped together as one peripheral compartment. Central compartment the central compartment includes the wellperfused organs and tissues heart, blood, liver, brain and kidney with which drug equilibrates rapidly.
Define various pharmacokinetic terms such as halflives, volume of. Introduction to pharmacokinetic models biopharmaceutics. Phar 7633 chapter 19 multicompartment pharmacokinetic. Pdf a single compartment simulation model of pharmacokinetics. Sep 02, 2014 mammillary model this is the most common compartment used in pharmacokinetics. The most simple pharmacokinetic model for describing the dissolution of the drug is an apparent volume within the body. The compartmental modeling of pharmacokinetics consists in describing the fate of a drug in the body, depicted as an entity divided into compartments.
The population pharmacokinetic analyses were performed using nonmem on concentrationtime data of glibenclamide, furosemide. Peripheral compartments the peripheral compartments includes those organs e. Instead, the concept focuses on broad types of fluidic. Pharmacokinetics model is the central piece of modelbased drug development. Phar 7633 chapter 19 multicompartment pharmacokinetic models. Pharmacokinetics biopharmaceutics multi compartment iv bolus 1. The substances of interest include any chemical xenobiotic such as. After an iv dose is administered, plasma concentrations rise and then rapidly decline as drug distributes out of plasma and into muscle tissue.
To compare the performance of the standard lag time model lag model with the performance of an analytical solution of the transit compartment model transit model in the evaluation of four pharmacokinetic studies with four different compounds. 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. Construction of percent absorbedtime plots based on the two compartment open model, drug intelligence 3. All the basic concepts of pharmacokinetics pks are described, with an emphasis on understanding what parameters such as bioavailability, volume of distribution and clearance tell us about the behaviour of a particular drug. The central compartment consists of plasma and highly perfused tissues in which drug distributes rapidly. Represent graphically the typical natural log of plasma drug concentration versus time curve for a onecompartment model after an intravenous dose. The absorption rate ka of olanzapine ranged from 2. V or v1, the volume of distribution in the central compartment. This metaanalysis was performed with a multivariate nonlinear mixed model.
Pharmacokinetics biopharmaceutics multi compartment iv. Phar 7633 chapter 8 pharmacokinetics of oral administration. 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. For most twocompartment models the elimination occurs from the central compartment model unless other information about the drug is known. Apply onecompartment pharmacokinetics to single and multiple. Pharmacokinetics of drugs following iv bolus, iv infusion, and oral. A pharmacokinetic model is a model devised to simulate the rate process of drug. Many drugs given in a single intravenous bolus dose demonstrate a plasma leveltime curve that does not decline as a single exponential firstorder process.
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. For threecompartment model equations, ct c 1t represent the drug concentration in the rst compartment, c 2t represents the drug concentration in the second compartment, and c 3t represents the drug concentration in the third compartment. For drugs to be effective they need to be able to move rapidly from blood plasma to other body fluids. The concentration profile could be best described using a two compartment model with firstorder absorption and elimination. Modeling of pharmacokinetics and pharmacodynamics with. This paper proposed an important approach to transform published non compartment model pharmacokinetics pk parameters into compartment model pk parameters. This paper proposed an important approach to transform published noncompartment model pharmacokinetics pk parameters into compartment model pk parameters. 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 noncompartment pharmacokinetics is a new approach devised to. Phar 7633 chapter 19 multicompartment pharmacokinetic models student objectives for this chapter to draw the scheme and write the differential equations appropriate to a multicompartment pharmacokinetic model to recognize and use the integrated equations for these models to calculate parameter values and for dosage regimen calculations. Clinical correlate digoxin, particularly when given intravenously, is an example of a drug that is well described by two compartment pharmacokinetics. Oct 03, 2016 introduction to pharmacokinetic models biopharmaceutics and pharmacokinetics. Learn compartment model pharmacokinetics with free interactive flashcards. Pharmacokinetics biopharmaceutics multi compartment iv bolus.
Model independent method overcomes some of the drawbacks associated with classical compartment modeling. Single blood compartment with fractional rates of absorption ka and elimination ke deterministic mathematical model individual pk behavior characterized by pk parameters. The plasma leveltime curve for a drug that follows a twocompartment model shows that the plasma drug concentration declines. This will suffice to introduce the general concepts of. Drug exhibits the characteristics of one compartment model. Pharmacodynamics research unit, the upjohn company, kalamazoo, michigan. Therefore, most pk propofol models consist of two or three compartments and a matching number of intercompartmental constants see fig.
The population pharmacokinetic analyses were performed using nonmem on concentrationtime data of. A multicompartment model capturing the pharmacokinetics. Twocompartment open model extra vascular administration firstorder absorption for a drug that enters the body by a firstorder absorption process and distributed according to twocompartment model, the rate of change in drug concentration in the central compartment is described by 3 exponents an absorption exponent, and the two usual. Pharmacokinetic models 7 cp a time log cp b time figure 1.
The fundamental concepts of pharmacokinetic modelling are described, including half. Thus, the onecompartment open model with iv bolus administration is the simplest pharmacokinetic model. 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. Mathematical expressions of the pharmacokinetic and pfim. These model plasma responses to an orallyadministered input when the input rate. Pharmacokinetics model is the central piece of model based drug development. Jan 05, 2011 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.
All the symbols imply is that, for a set of values of a dependent variable, there is some. A multicompartment model capturing the pharmacokinetics of the calcimimetic cinacalcet gudrun schappachertilpa doris h. Mathematical expressions of the pharmacokinetic and. Over 30 clinical cases with selfstudy questions and answers are presented throughout to bridge the gap between pharmacokinetic concepts and their practical application to individual patients. To fulfill the model based drug development, the very first step is usually a model establishment from published literatures. Fuertingerb peter kotankoc,d auniversity of graz, institute of mathematics and scientific computing, graz, austria, bfresenius medical care germany, global research and development, bad homburg, germany, crenal research. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient.
Jun 12, 2017 pharmacokinetics biopharmaceutics multi compartment iv bolus 1. Basic assumption is that drug or metabolite follows. Introduction to pharmacokinetic models biopharmaceutics and. Choose from 152 different sets of compartment model pharmacokinetics flashcards on quizlet. Dec 12, 2016 introduction to open compartment iv bolus pharmacy fun. Compartmental model analysis in pharmacokinetics fleishaker. Pharmacokinetic models one, two, multicompartment dosing calculations once absorbed, a drug molecule is subject to. Implementation of a transit compartment model for describing. The model consists of one or more peripheral compartments connected to a central compartment.
The fundamental principles of compartmental pharmacokinetics. For one compartment body model if the dosing involves the use of i. It is performed by noncompartmental or compartmental methods. In pharmacokinetics, a compartment is a defined volume of body fluids, typically of the human body, but also those of other animals with multiple organ systems. Pharmacokinetics was defined as 12 of pharmacology. Phar 7633 chapter 8 pharmacokinetics of oral administration scheme or diagram this model can be represented as.
Two compartment pharmacokinetic model with effect compartment e to model pharmacodynamics. 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. Dec 23, 2016 the fundamental concepts of pharmacokinetic modelling are described, including half. View the article pdf and any associated supplements and figures for a period of 48 hours.
Details of the model will depend on the specific drug. Twocompartment pharmacokinetic model with effect compartment e to model pharmacodynamics. Rate of elimination is proportional to the amount in bloodplasma. Peripheral compartment s the peripheral compartment s includes those organs e. The meaning in this area of study is different from the concept of anatomic compartments, which are bounded by fasciae, the sheath of fibrous tissue that enclose mammalian organs.
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