Clinical pharmacokinetics and pharmacodynamics larry a. You can import into simbiology pharmacokinetics software pk and pd data of various sorts, including text files, microsoft excel files, and matlab files. Pharmacokinetics pk is talked about a lot in the hiv community. Area under the curve and bioavailability sciencedirect.
Figures 24 and 25 repr esent two ways of thinking about drug clearance. A peak at pk an introduction to pharmacokinetics lex jansen. The definite integral can be used to find the area between a graph curve and the x axis, between two given x values. Combining pharmacokinetics pk and pharmacodynamics pd gives an overall picture of the drug response.
Quizlet flashcards, activities and games help you improve your grades. Also, you can add more pdfs to combine them and merge them into one single document. Aaps advances in the pharmaceutical sciences series, vol. More specifically, it is the timeaveraged concentration of drug circulating in the body fluid analyzed normally plasma, blood or serum. Standard calculation of auc involves using noncompartmental techniques to calculate the auc from. The equations and a majority of introductory concepts presented in the reading handout may be. Glossary of terms and symbols used in pharmacology. Jan 22, 2014 contents of the powerpoint on non compartmental pharmacokinetics include. Binding to plasma proteins will increase the rate of passive absorption by maintaining the concentration gradient of free drug. The area under the plot of plasma concentration of drug not logarithm of the concentration against time after drug administration. Ppt pharmacokinetics calculations powerpoint presentation. Population pharmacokinetics poppk characterize pk and pd in target patient population using sparse sampling and pharmacostatistical methodologies.
Area under the curve auc analysis used to determine f f auc area under blood concentration. The area under the moment curve aumc from the time of dosing to the last measurable concentration. Area under the plasma concentrationtime curve zero, first, secondorder kinetics plasma halflife. Use the accompanied applet and worksheet to develop formula for the area under a curve. The total amount of drug eliminated by the body may. All the four processes involve drug movement across the membranes. In a drug with nonlinear kinetics, doubling the dose will double the concentration. Perfluorooctanoic acid pfoa and related compounds are used primarily as surfaceactive agents in the production of various fluoropolymers and fluoroelastomers kudo and kawashima, 2003. Deals with relationship of drug dose and conc of drug in body over time important relationship between drug dosage, pharmacokinetic processes, and pharmacological response with respect to plasma drug concentration cp.
Pharmacokinetics of a drug depends on patientrelated factors as well as on the drugs chemical properties. Pdf pharmacokinetics, distribution, metabolism, and. The fundamental principles of compartmental pharmacokinetics. Scribd is the worlds largest social reading and publishing site. Basic pharmacokinetics 21 cate the amount of drug being removed. By integrating over time rather than looking at individual concentration measurements, a more accurate estimate of the overall exposure to the drug. In practice, the drug concentration is measured at certain discrete points in time and the trapezoidal rule is. The auc is calculated by computer or by the trapezoidal method, wherein the entire curve is divided. Auc dr nirav, md pharmacology, jamnagar it is only in the mysterious equations of love that any logical reasons can be found quote from movie a beautiful mind 2. Bioavailability f is a measure of the systemic availability of a drug administered by a route other than iv. This area under the curve is dependant on the rate of elimination of the drug from the body and the dose administered. Area under the curve dr ashwin r linkedin slideshare. Diagnostic and statistical manual of mental disorders, 4th ed. Overview of pharmacokinetics clinical pharmacology msd.
Professor of clinical pharmacology, flinders university of south australia, adelaide. 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. Area under the curve or auc is a pharmacokinetic statistic used to describe the total exposure to a drug. Evaluate the steadystate auc area under curve and mean trough of serum total igg for subcutaneously administered gamunexc compared to that. Pharmacokinetics basics absorption, distribution, metabolism. In pharmacology, the area under the plot of plasma concentration of a drug versus time after dosage called area under the curve or auc gives insight into the extent of exposure to a drug and its clearance rate from the body. Mar 14, 20 the area under the concentrationtime curve extrapolated to infinity auc 0. The basic calculations are based on the area under the plasma concentration versus times curve zero moment and the first moment curve aumc. Some patientrelated factors eg, renal function, genetic makeup, sex, age can be used to predict the pharmacokinetic parameters in populations. Students like that each chapter includes sample problems. An additional pharmacokinetic metric for bioavailability and bioequivalence assessments.
In addition, the pharmacokinetics of elimination by the kidneys of certain radiopharmaceuticals e. Drug binding many drugs will bind strongly to proteins in the blood or to food substances in the gut. The following pharmacological definition has been taken from the pharmacology and experimental therapeutics department glossary at boston university school of medicine. D department of pharmaceutics kle university s college of pharmacy a free powerpoint ppt presentation displayed as a flash slide show on id. It is of interest to know the area under the curve, i. Graphpad prism 7 statistics guide area under the curve. In practice, the drug concentration is measured at certain discrete points in time and the trapezoidal rule is used to estimate auc. The area under the plasma drug concentrationtime curve auc reflects the actual body exposure to drug after administration of a dose of the drug and is expressed in mghl. The area under the curve auc is commonly used to assess the extent of exposure of a drug. Explain the meaning of the terms absorption, distribution, metabolism, and excretion. It indicates the volume of plasma or blood from which the drug is completely removed, or cleared, in a given time period.
Pharmacokinetics describes how the body affects a specific xenobioticchemical after administration through the mechanisms of absorption and distribution, as well as the metabolic changes of the substance in the body e. Pharmacokinetics of free and total mycophenolic acid in adult lupus. It is the measure of the rate kinetics of absorption, distribution, metabolism and excretion adme. The aumc is the area under the concentration times time versus. The same concept can be applied to generally assess pharmacodynamic responses and the deviation of a signal from its baseline value. It represents the area under the plasma concentration curve, also called the plasma concentrationtime profile. Based on pharmacokineticspharmacodynamics pkpd and the minimum.
Modeling of pharmacokinetics and pharmacodynamics with. Phenytoin needs to be given twice or 3 times daily because it has a halflife of about 12 hours. The first moment is calculated as concentration times time cp t. Assessment of pharmacologic area under the curve when. Area under a curveusing a limit since letting n be a very large number will result in a huge amount of work, the process can be simplified by using sigma notation and summation formulas to create a riemann sum. The library of pharmacokinetic pk and pharmacodynamic pd models described in this. By dragging your pages in the editor area you can rearrange them or delete single pages. This article is within the scope of wikiproject pharmacology, a collaborative effort to improve the coverage of pharmacology on wikipedia. The medicine is chosen on the basis of an evidencebased approach to clinical practice and assured to be compatible with. Pharmacokinetics is the science describing drug absorption from. Nonlinear leastsquares regression analyses determined the pkpd index the maximal unbound drug concentration fcmaxmic, the area under the unbound drug concentrationtime curve faucmic, or the percentage of a 24h time period that the unbound drug concentration exceeds the mic ftmic that was most predictive of the effect. Patients need to be prescribed appropriate medicines for a clinical condition. The estimated area under the concentrationtime curve from 0 to 12 h.
This area is called the area under the curve regardless of whether it is above or below the x axis. 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. Importance of auc pharmacokinetics measurement of bioavaibility absolute, relative biopharmaceutics comparison of drug products in babe studies calculation of pk parameters 5. The absorption, distribution, and excretion of drugs objectives after studying this chapter, the reader should be able to. Apr 09, 2011 pharmacokinetics is the way the body acts on the drug once it is administered. Stub this article has been rated as stubclass on the projects quality scale. The auc can be calculated as before using by the trapezoidal rule. In pkpd it is assumed that the drug concentration is the driving force of the pharmacological e.
Oct 30, 2010 pharmacokinetics auc area under curve 1. Pharmacokinetic modeling and optimal sampling strategies for. To be able to cross the membranes it is necessary that the drugs should be able dissolve directly. A pkpd experiment consists of pharmacokinetic and pharmacodynamic measurements performed in a population of individuals. The auc is a measure of total systemic exposure to the drug. Giltinan, in encyclopedia of biostatistics, 2nd edition 6. Large number of subjects 100, up to thousands oral dose. Auc area under the curve a measure of the exposure to the drug. Pharm pharmacokinetics definitions study guide by broadband109 includes 30 questions covering vocabulary, terms and more. Modeling single and repeated dose pharmacokinetics of pfoa. Area under the plasma concentration time curve auc.
Pk is the study of what the human body does to drugs to get the drug out of the body. C1 time profile is regarded as expressions of exponents c1 time profile is regarded as statistical distribution. Pharm pharmacokinetics definitions flashcards quizlet. Area under the curve from 0 to infinity aucifo when using clast. Bioavailability f is a measure of the systemic availability of a drug administered by a route other than intravenous. Clinical pharmacokinetics is the discipline that describes the absorption, distribution, metabolism, and elimination of drugs in patients requiring drug therapy. For many drugs, the gastrointestinal absorption rate, but not the. Meperidine and morphine presumably combine with the same receptors to. Pdf pharmacokinetics of total and unbound ertapenem in. Noncompartmental pharmacokinetics and bioequivalence analysis. Pharmacokinetics pk what the body does to the drug pharmacodynamics pd what the drug does to the body an outstanding overview. An intermediate merged input dataset is created for pk concentrations based on the clinical dm, ex. You can also import data from other sources, such as databases or sas files, using the matlab workspace as an intermediate.
The equations and a majority of introductory concepts presented in. Area under the plasma concentrationtime curve zero. Mathematical expressions of the pharmacokinetic and. Pharmacokinetic training packet for pharmacists revised 109, 612 original document compiled by.
A single oral dose of 300 mg bioequivalent to 100 mg iv of omadacycline administered to fasted subjects achieved a maximum plasma concentration cmax of 0. Curve fitting of experimental data using computers. Clearance is the most important pharmacokinetic parameter because it determines the steadystate concentration for a given dosage rate. The area under the curve is an integrated measurement of a measurable effect or phenomenon. Area under the concentration time curve from 0 to 2 h auc02 and free fraction. The area is conveniently determined by the trapezoidal rule. Overview of pharmacokinetics clinical pharmacology. Evaluation of the ratio of the estimated area under the concentration. List two physiologic factors that can alter each of the processes of absorption, distribution, and excretion.
A study to evaluate the pharmacokinetics and the effect on. Tp made substantial contributions to the conception and design of the work, the acquisition of data as well as revising the manuscript. Effect of extremes of body weight on the pharmacokinetics. Whole organ pharmacokinetics are used to estimate the mean residence times of radioactivity and from these, the radiation absorbed doses deposited in various tissues following administration of a radiopharmaceutical 4.
It is used as a cumulative measurement of drug effect in pharmacokinetics and as a means to compare peaks in chromatography. Areas under the concentrationtime curve from 0 h to infinity auc0. The area under the plasma drug concentrationtime curve auc reflects the actual. Clinical pharmacokinetics deals with relationship of drug dose and conc of drug in body over time important relationship between drug dosage, pharmacokinetic processes, and pharmacological response with respect to plasma drug concentration cp. Davidsonx d001x medicinal chemistry chapter 7 pharmacokinetics part 3 clearance ii video clip area under curve drugs with a lower clearance persist for a longer time in the body.
Drugs with a higher clearance persist for a shorter time in the body. No curve fitting and no computers applicable to linear and nonlinear pharmacokinetics applicable to linear pharmacokinetics. The most current, handson book in the field, applied clinical pharmacokinetics the perfect textbook for pharmacy students learning the clinical application of pharmacokinetics, which is the mathematical tools for modifying doages. A linear relationship exists between area under the curve and dose when the. The percent of the observed area under the first moment curve aumc that is extrapolated to infinity.
Knowing the bioavailability and the dose, the clearance of the drug may be. One determines bioavailability by comparing the area under the plasma drug concentration curve versus time auc, area under the curve for the extravascular formulation to the auc for the intravenous formulation. In the field of pharmacokinetics, the area under the curve auc is the definite integral of a curve that describes the variation of a drug concentration in blood plasma as a function of time. Principles of pharmacokinetics learning objectives. The area under the curve auc is proportional to the fraction absorbed only if the clearance is constant and the concentration uniform. Because of the strength of the carbonfluorine bond, pfoa is stable to metabolic and environmental degradation butenhoff et al. The auc 0infinity is the area under the plasma concentrationtime curve from time zero to infinite time, calculated as the sum of auc0last and clastlambdaz. To merge pdfs or just to add a page to a pdf you usually have to buy expensive software. Jul 18, 2014 shargel l, yu a 1999 applied biopharmaceutics and pharmacokinetics, 4th edn.
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