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. Pharmacokinetics are classically represented by compartment models, such as the onecompartment model shown to the right. Once a drug is administered, we usually describe subsequent processes within the organism by the pharmacokinetics pk process known as adme. Jan 22, 2014 contents of the powerpoint on non compartmental pharmacokinetics include. Eur rev med pharmacol a short introduction to pharmacokinetics. The best and the simplest way of estimating vd of a drug is administering it by rapid i. Of drug in various body fluids with dosage regimen. The model is called open model because the drug can be eliminated fig. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Onecompartment model following drug administration, the body is depicted as a kinetically homogeneous unit see figure 1.
The library of pharmacokinetic pk and pharmacodynamic pd models described in this. Simultaneous fit to three lines after three different iv doses. 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. 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. Hopefully you now understand what is meant by compartmental models in pharmacokinetics. Facilitates simulation from hierarchical, ordinary differential equation ode based models typically employed in drug development. Curve fitting of experimental data using computers. Many may be asking why we use compartment models in pharmacokinetics.
The equations in the ensuing chapter describe the pharmacokinetic models. Compartment models also called as empirical models. 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. Pharmacokinetics of pentoxyphylline and its major active metabolites was. These models simply interpolate the experimental data and allow an empirical formula to estimate the drug concentration with time.
Absorption is the movement of the drug into the bloodstream from an extravascular site. Two different approaches for pharmacokinetic modelling are presented. 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. Pharmacokinetic models are relatively simple mathematical schemes that represent complex physiologic spaces or processes. In the general case of ncompartmental models as was conceived. 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.
Mathematical expressions of the pharmacokinetic and pfim. In essence, the number 1, 2, 3 refers to the number of circles drawn on the paper. Pharmacodynamic models deal with the action of the drug once it reaches its target organ. For this comparison, assume that you are modeling administration of a drug using a twocompartment model with any dosing input and linear elimination. Figures 24 and 25 repr esent two ways of thinking about drug clearance. Pharmacokinetics of drugs with saturable clearance is usually described by the michaelsmenten mm equation 1, 2. However a complete and versatile pharmacokinetic description of remifentanil still lacks. 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. 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. The purpose of this continuing education lesson is to illustrate with examples of radiopharmaceuticals commonly used in nuclear medicine the fundamental principles of pharmacokinetics. For cases where a saturable clearance andor distribution process is controlled by the pharmacological target of the drug e. Noncompartmental versus compartmental approaches to.
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. Compartment models noncompartment models these require elaborate assumptions to fit the data do not require assumptions to compartment model. Pharmacodynamic models implemented in the pfim software anne dubois, julie bertrand and france mentr e umr738, inserm, university paris diderot programmer. Compartmental systems proved to be useful models in various biological domains including physiology, pharmacokinetics, population dynamics, and epidemiology 5, 15, 18. A statistical analysis of plasma concentration time data is another method used to find out no of compartments. The brief answer is that the mathematical functions associated with compartment models seem to describe. Apply onecompartment pharmacokinetics to single and multiple. It indicates the volume of plasma or blood from which the drug is completely removed, or cleared, in a given time period. Introduction to pharmacokinetics and pharmacodynamics ashp. Within each compartment drug is distributed uniformly. Vd is a measure of the extent of distribution of drug and is expressed in liters.
Pharmacokinetics pk what the body does to the drug pharmacodynamics pd what the drug does to the body an outstanding overview. 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. The attraction of the onecompartment model is its simplicity. Two different approaches for pharmacokinetic modeling of exhaled. 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. Compartmental analysis is the traditional and most commonly used approach to pharmacokinetic characterization of a drug. 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.
The compartmental modeling of pharmacokinetics consists in describing the fate of a drug in the body, depicted as an entity divided into compartments. In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination. Pharmacokinetic models predict the time dependence of a drugs concentration in the body fluids following its administration. Gibaldi pharmacokinetics, 2nd edition, pg no 409417 leon shargel,applied biopharmaceutics and pharmacokinetics,5th edition,pg no 717753 v. Fitting compartmental models fitting ttacs plasma pharmacokinetics area under curve. Clearance and apparent volume of distribution are two. Mammillary model this is the most common compartment used in pharmacokinetics.
Usually a 3compartment model is used for pharmacokinetic. 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. Assumptions of compartmental models the body is represented as a series of compartment arranged in series or parallel to each other. A wellcharacterized pkpd model is an important tool in guiding the design of future experiments and trials.
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. Accurate pk modeling is important for precise determination of elimination rate. No curve fitting and no computers applicable to linear and nonlinear pharmacokinetics. Phar 7633 chapter 19 multicompartment pharmacokinetic models. Modeling pharmacokinetic data using computer programs such as boomer. For each model the equation for cet is given after the corresponding one for ct. Pharmacokinetic models are hypothetical structures that are used to describe the. 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. Apply one compartment pharmacokinetics to single and multiple. Introduction to pharmacokinetics and pharmacodynamics. Pharmacokinetic models pharmacokinetic models are hypothetical structures that are used to describe the fate of a drug in a biological system following its administration.
Mathematical expressions of the pharmacokinetic and. Pharmacokinetics models pharmacokinetics plays an important role in the determination of drug action within the living organism. The fundamental principles of compartmental pharmacokinetics. 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. 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. Ordinary differential equations odes for this ncompartmental model are. 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. The rate of drug movement between compartment is described by first order kinetics. Rate constants are used to represent rate of entry into and exit from compartment. Pharmacokinetics studies the time course of absorption, distribution, metabolism, and elimination of some substance in the body, given a drug dose, i. Evaluating pharmacokinetic and pharmacodynamic interactions. Basic pharmacokinetics 21 cate the amount of drug being removed. 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. Jan 05, 2011 the 2 key differences are that the pharmacokinetic models are not closed systems drug is not recirculated from output to input.
Pharmacokinetics refers to the rate and extent of distribution of a drug to different tissues, and the. Venkateshwarlu,biopharmaceutics and pharmacokinetics, pg no 309330. Selection between michaelismenten and targetmediated drug. Compartmental model analysis in pharmacokinetics fleishaker. View the article pdf and any associated supplements and figures for a period of 48 hours. Sep 30, 2014 pharmacokinetic models means of expressing mathematically or quantitatively, time course of drug through out the body and compute meaningful pharmacokinetic parameters. For many drugs, the gastrointestinal absorption rate, but not the. Pharmacokinetics and pharmacodynamics in renal disease. Useful pharmacokinetic equations uf college of pharmacy. 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. 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.
Pharmacokinetics modelling list of high impact articles. Pharmacodynamic models describe how a drug affects the body by linking the drug concentration to an efficacy or safety metric. Modeling of pharmacokinetics and pharmacodynamics with. Drug binding many drugs will bind strongly to proteins in the blood or to food substances in the gut. Noncompartmental pharmacokinetics and bioequivalence analysis. Represent graphically the typical natural log of plasma drug concentration versus time curve for a onecompartment model after an intravenous dose. When analyzing pharmacokinetic data, one generally employs either model fitting.
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