Pharmacodynamic models implemented in the pfim software anne dubois, julie bertrand and france mentr e umr738, inserm, university paris diderot programmer. Figures 24 and 25 repr esent two ways of thinking about drug clearance. Compartmental model analysis in pharmacokinetics fleishaker. Compartment models noncompartment models these require elaborate assumptions to fit the data do not require assumptions to compartment model. While the answer to the question for many of the simpler models used in pharmacokinetics is well known, the general answer, even for linear, constantcoefficient models, is more difficult. Pbpk models of chemical mixtures involve the change of rates of adme for one or more chemicals. Giltinan, in encyclopedia of biostatistics, 2nd edition 6. 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. Absorption is the movement of the drug into the bloodstream from an extravascular site. Once a drug is administered, we usually describe subsequent processes within the organism by the pharmacokinetics pk process known as adme. Mathematical expressions of the pharmacokinetic and. The model is called open model because the drug can be eliminated fig. In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination.
Pharmacodynamic models deal with the action of the drug once it reaches its target organ. In the general case of ncompartmental models as was conceived. How simbiology models represent pharmacokinetic models the following figure compares a model as typically represented in pharmacokinetics with the same model shown in the simbiology model diagram. The equations in the ensuing chapter describe the pharmacokinetic models. Pharmacokinetic modeling approaches there are three approaches that have been suggested for pharmacokinetic modeling, compartmental model physiological model model independent approach compartmental model the first is an empirical approach, which is based on a simple compartmental model. Modeling pharmacokinetic data using computer programs such as boomer. Clearance and apparent volume of distribution are two. Introduction to pharmacokinetics and pharmacodynamics ashp. Compartment models also called as empirical models. Pharmacokinetics of pentoxyphylline and its major active metabolites was.
Evaluating pharmacokinetic and pharmacodynamic interactions. Hopefully you now understand what is meant by compartmental models in pharmacokinetics. When analyzing pharmacokinetic data, one generally employs either model fitting. In essence, the number 1, 2, 3 refers to the number of circles drawn on the paper. Mathematical expressions of the pharmacokinetic and pfim. Pharmacodynamic models describe how a drug affects the body by linking the drug concentration to an efficacy or safety metric. Pharmacokinetics of drugs with saturable clearance is usually described by the michaelsmenten mm equation 1, 2. Pharmacokinetics models pharmacokinetics plays an important role in the determination of drug action within the living organism. Simultaneous fit to three lines after three different iv doses. Pharmacokinetic models are relatively simple mathematical schemes that represent complex physiologic spaces or processes. Venkateshwarlu,biopharmaceutics and pharmacokinetics, pg no 309330. Accurate pk modeling is important for precise determination of elimination rate.
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. Jan 22, 2014 contents of the powerpoint on non compartmental pharmacokinetics include. Represent graphically the typical natural log of plasma drug concentration versus time curve for a onecompartment model after an intravenous dose. Binding to plasma proteins will increase the rate of passive absorption by maintaining the concentration gradient of free drug. The library of pharmacokinetic pk and pharmacodynamic pd models described in this. Pharmacodynamics research unit, the upjohn company, kalamazoo, michigan. For each model the equation for cet is given after the corresponding one for ct. For many drugs, the gastrointestinal absorption rate, but not the.
Mathematical expressions of the pharmacokinetic and pharmacodynamic models implemented in the pfim software anne dubois, julie bertrand and france mentr e umr738, inserm, university paris diderot programmer. Pharmacokinetics and pharmacodynamics in renal disease. Pharmacokinetics studies the time course of absorption, distribution, metabolism, and elimination of some substance in the body, given a drug dose, i. Two different approaches for pharmacokinetic modelling are presented. The library of pharmacokinetic pk and pharmacodynamic pd models described in. Noncompartmental pharmacokinetics and bioequivalence analysis.
Pharmacokinetics are classically represented by compartment models, such as the onecompartment model shown to the right. These models simply interpolate the experimental data and allow an empirical formula to estimate the drug concentration with time. Selection between michaelismenten and targetmediated drug. Drug binding many drugs will bind strongly to proteins in the blood or to food substances in the gut. Pharmacokinetic models are hypothetical structures that are used to describe the. The rate of drug movement between compartment is described by first order kinetics. Phar 7633 chapter 19 multicompartment pharmacokinetic models effect of k12 and k21 on drug concentration versus time changing the ratio of k12 to k21 figure 19. Using models, new meaningfull pharmacokinetic parameters may be defined which can be used to find relationships between the drug kinetic profile and the physiological process which drive the drug absorption, distribution and elimination. Apply onecompartment pharmacokinetics to single and multiple. The purpose of this continuing education lesson is to illustrate with examples of radiopharmaceuticals commonly used in nuclear medicine the fundamental principles of pharmacokinetics. Pharmacokinetics refers to the rate and extent of distribution of a drug to different tissues, and the. Types of compartment models based on whether the compartment is arranged in parallel or series the compartmental models are classified into four types they are. 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.
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. A statistical analysis of plasma concentration time data is another method used to find out no of compartments. No curve fitting and no computers applicable to linear and nonlinear pharmacokinetics. Curve fitting of experimental data using computers. Mammillary model this is the most common compartment used in pharmacokinetics.
Pharmacokinetic models pharmacokinetic models are hypothetical structures that are used to describe the fate of a drug in a biological system following its administration. In practice, it is generally considered that steady state is reached when a time of 4 to 5 times the halflife for a drug after regular dosing is started. The fundamental principles of compartmental pharmacokinetics. The best and the simplest way of estimating vd of a drug is administering it by rapid i. Compartmental analysis is the traditional and most commonly used approach to pharmacokinetic characterization of a drug. Useful pharmacokinetic equations uf college of pharmacy. Sep 30, 2014 pharmacokinetic models means of expressing mathematically or quantitatively, time course of drug through out the body and compute meaningful pharmacokinetic parameters. Pharmacokinetics modelling list of high impact articles. Basic pharmacokinetics 21 cate the amount of drug being removed. Two different approaches for pharmacokinetic modeling of exhaled. Apply one compartment pharmacokinetics to single and multiple. Usually a 3compartment model is used for pharmacokinetic. However a complete and versatile pharmacokinetic description of remifentanil still lacks.
For cases where a saturable clearance andor distribution process is controlled by the pharmacological target of the drug e. Fitting compartmental models fitting ttacs plasma pharmacokinetics area under curve. Assumptions of compartmental models the body is represented as a series of compartment arranged in series or parallel to each other. Jan 05, 2011 the 2 key differences are that the pharmacokinetic models are not closed systems drug is not recirculated from output to input.
Vd is a measure of the extent of distribution of drug and is expressed in liters. K 12 and k 21 are used to represent the constants for transfer of drug from central to peripheral and from peripheral to central compartment respectively. Introduction to pharmacokinetics and pharmacodynamics. Twocompartmentbody model cae be tt auc a b vd vd vcarea ss creatinine clearance cl male age weight creat cp creat 140 72 cl female age weight creat cp creat 140 85 with weight in kg, age in years, creatinine plasma conc. Pharmacokinetics pk what the body does to the drug pharmacodynamics pd what the drug does to the body an outstanding overview. It indicates the volume of plasma or blood from which the drug is completely removed, or cleared, in a given time period. Facilitates simulation from hierarchical, ordinary differential equation ode based models typically employed in drug development. Rate constants are used to represent rate of entry into and exit from compartment.
Onecompartment model following drug administration, the body is depicted as a kinetically homogeneous unit see figure 1. 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. Pharmacokinetic models predict the time dependence of a drugs concentration in the body fluids following its administration. Noncompartmental versus compartmental approaches to.
Ordinary differential equations odes for this ncompartmental model are. Modeling of pharmacokinetics and pharmacodynamics with. Phar 7633 chapter 19 multicompartment pharmacokinetic models. A wellcharacterized pkpd model is an important tool in guiding the design of future experiments and trials. Within each compartment drug is distributed uniformly. Today, increased physiologic understanding of pharmacokinetics shows that halflife is a secondary parameter that depends upon the primary parameters clearance and apprent volume of distribution according to following equation. 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 alteration of the absorptionexcretion rate of a chemical as a result of the presence of other chemicals is often caused by interference with an active uptakeexcretion process or by modulation of critical biological determinants of uptake e. For this comparison, assume that you are modeling administration of a drug using a twocompartment model with any dosing input and linear elimination. Compartmental systems proved to be useful models in various biological domains including physiology, pharmacokinetics, population dynamics, and epidemiology 5, 15, 18.