You can also perform statistical analyses on the data, such as calculating the mean, area under the curve auc, area under the first moment curve. Doseresponse relationships msd manual professional edition. Area under the curve auc analysis used to determine f f auc area under blood concentration. Figures 24 and 25 repr esent two ways of thinking about drug clearance. Distribution, metabolism, and excretion of drugs in the. In practice, the drug concentration is measured at certain discrete points in time and the trapezoidal rule is used to estimate auc. By integrating over time rather than looking at individual concentration measurements, a more accurate estimate of the overall exposure to the drug. Oct 30, 2010 pharmacokinetics auc area under curve 1. Pharmacokinetics getting to the target pharmacodynamics action at the target now look at pharmacokinetics in a more practical, quantitative sense. To measure the bioavailability of an iv injection, you must use the area under the plasma concentrationtime curve and the portion of area under the iv curve in your equation. 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. 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.
The area under the plasma concentration versus time curve, also called the area under the curve auc, ends up being an extremely useful parameter in pk. Pharmacokinetics, absorption and tissue distribution of. Statistics and pharmacokinetics in clinical pharmacology. C1 time profile is regarded as expressions of exponents c1 time profile is regarded as statistical distribution. 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. The same concept can be applied to generally assess pharmacodynamic responses and the deviation of a signal from its baseline value. Statistics and pharmacokinetics in clinical pharmacology studies. The area under the plasma drug concentrationtime curve auc reflects the actual. The equations and a majority of introductory concepts presented in the reading handout may be.
In nonclinical pk studies, it is often the case that experimental units contribute data for only a single time point. The models used in nonlinear pharmacokinetics are largely based on michaelismenten kinetics. The saturation of capacitylimited processes may be. Study to assess the absorption, metabolism, excretion and pharmacokinetics of 14cakb9778 the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Patients need to be prescribed appropriate medicines for a clinical condition. This area under the curve is dependant on the rate of elimination of the drug from the body and the dose administered. If the pharmacokinetic data were estimated only from the blood levels described by curve b, then a twofold increase in the dose would give the blood profile presented in curve c, which considerably. The area under the curve auc is proportional to the fraction absorbed only if the clearance is constant and the concentration uniform. Graphpad prism 7 statistics guide area under the curve. Only the areas of the zero and first moments are generally used in pharmacokinetic anal ysis, because the higher. Study to assess the absorption, metabolism, excretion and. The absorption, distribution, and excretion of drugs objectives after studying this chapter, the reader should be able to.
Pharmacokinetics parameters area under the curve auc. In pharmacology, the area under the plot of plasma concentration of a drug versus time after dosage called area under the curve or auc. The library of pharmacokinetic pk and pharmacodynamic pd models described in this. Explain the meaning of the terms absorption, distribution, metabolism, and excretion. Students like that each chapter includes sample problems. In the field of pharmacokinetics, the area under the curve is the definite integral of a curve that describes the variation of a drug concentration in blood plasma as a function of time.
Eur rev med pharmacol a short introduction to pharmacokinetics. Estimation of the areaunderthecurve of mycophenolic. Pharmacokinetics from ancient greek pharmakon drug and kinetikos moving, putting in motion. Area under the plasma concentrationtime curve zero, first, secondorder kinetics plasma halflife. It represents the area under the plasma concentration curve, also called the plasma concentrationtime profile. It is of interest to know the area under the curve, i. 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. 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. C3 model c0 0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60. Excluding a data point does not remove it from the data set permanently, but rather flags the data point to be ignored during analysis. Importance of auc pharmacokinetics measurement of bioavaibility absolute, relative biopharmaceutics comparison of drug products in babe studies calculation of pk parameters 5. Principles of pharmacokinetics learning objectives. Area under the curve, bioavailability, and clearance. This area is called the area under the curve regardless of whether it is above or below the x axis.
Mathematical expressions of the pharmacokinetic and. In addition, the pharmacokinetics of elimination by the kidneys of certain radiopharmaceuticals e. Some drugs are not affected by food, while the absorption of a third group of drugs is enhanced by food bile secretion by liver in response to food in gi tract increases drug absorption. Shaw, biomarker research laboratory, university of pennsylvania, philadelphia, pa. The graph for the nonlinear relationship between the various factors is represented by a curve. Auc is the area under the curve describing the drug concentration as a function of time, and is a measure of. Pharmacokinetics getting to the target pharmacodynamics action at the target. 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. Bioavailability f is a measure of the systemic availability of a drug administered by a route other than intravenous. It represent the total integrated area under the plasma leveltime profile and expresses the total amount of drug that comes into the systemic circulation after its. Notice that the drug concentrations in urines are very rarely of interest in pharmacokinetics even if this is what is measured directly, but the drug amounts.
The auc is calculated by computer or by the trapezoidal method, wherein the entire curve is divided. Pharmacokinetics describes the movement greek kinesis of a. In practice, the drug concentration is measured at certain discrete points in time and the trapezoidal rule is. 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 area under the curve is an integrated measurement of a measurable effect or phenomenon. No gender effect was observed and no serious adverse events were reported. D department of pharmaceutics kle university s college of pharmacy a free powerpoint ppt presentation displayed as a flash slide show on id. Pharmacokinetics drug auc values can be used to determine other pharmacokinetic parameters, such as clearance or bioavailability, f. The best available pharmacokinetic parameter to be monitored is the area under the curve auc on the plot of measured drug concentrations versus time, over the entire dosing interval. Because a drug effect is a function of dose and time, such a graph depicts the doseresponse relationship independent of time. Knowing the bioavailability and the dose, the clearance of the drug may be. 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. More specifically, it is the timeaveraged concentration of drug circulating in the body fluid analyzed normally plasma, blood or serum.
Describe the physicochemical and physiological factors that influence the absorption of drugs from enteral and parenteral routes of administration, their distribution within the body, and their routes and mechanisms of elimination. Curve fitting of experimental data using computers. Pharmacokinetics was defined as 12 of pharmacology. The substances of interest include any chemical xenobiotic such as. Area under the curve an overview sciencedirect topics. Area under the curve pharmacokinetics wikivisually. Doseresponse data are typically graphed with the dose or dose function eg, log 10 dose on the xaxis and the measured effect response on the yaxis. List two physiologic factors that can alter each of the processes of absorption, distribution, and excretion. This study was designed to elucidate the pharmacokinetics, absorption, tissue distribution and plasma protein binding properties of tanshinone iia, a highly lipophilic compound isolated from salvia miltiorrhiza. The area under the curve auc is not proportional to the amount of bioavailable drug. In addition, pharmacokinetics is a valuable adjunc for prescribing and evaluating drug therapy. The area under the curve auc is commonly used to assess the extent of exposure of a drug. The area under the curve auc of the concentrationtime curve for a drug or metabolite, and the variation associated with the auc, are primary results of most pharmacokinetic pk studies.
It is used as a cumulative measurement of drug effect in pharmacokinetics and as a means to compare peaks in chromatography. 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. Atkinson pharmacokinetics is an important tool that is used in the conduct of both basic and applied research, and is an essential component of the drug development process. Area under the curve or auc is a pharmacokinetic statistic used to describe the total exposure to a drug. The medicine is chosen on the basis of an evidencebased approach to clinical practice and assured to be compatible with.
Some drugs are not affected by food, while the absorption of a third group of drugs is enhanced by food bile secretion by liver in response to food in. The definite integral can be used to find the area between a graph curve and the x axis, between two given x values. No curve fitting and no computers applicable to linear and nonlinear pharmacokinetics applicable to linear pharmacokinetics. Estimation of confidence intervals for area under the curve. In such cases, it is straightforward to apply noncompartmental methods to determine an. Drugs with a higher clearance persist for a shorter time in the body. In addition, pharmacokinetics is a valuable adjunc for. Basic pharmacokinetics 21 cate the amount of drug being removed.
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. The area under the plot of plasma concentration of drug not logarithm of the concentration against time after drug administration. 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. Area under the curve and bioavailability sciencedirect. It indicates the volume of plasma or blood from which the drug is completely removed, or cleared, in a given time period. Pharmacokinetics calculation free download as powerpoint presentation. Assessment of pharmacologic area under the curve when. Plasma concentrationtime curve an overview sciencedirect. 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. Pdf pharmacokinetics of total and unbound ertapenem in. The total amount of drug eliminated by the body may. Ppt pharmacokinetics calculations powerpoint presentation. The area is conveniently determined by the trapezoidal rule. Estimation of confidence intervals for area under the.
The auc is a measure of total systemic exposure to the drug. 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. Pdf pharmacokinetics, distribution, metabolism, and. Standard calculation of auc involves using noncompartmental techniques to calculate the auc from. The equations and a majority of introductory concepts presented in. For many drugs, the gastrointestinal absorption rate, but not the extent of absorption, is reduced by the presence of food in the gut. Area under the plasma concentration time curve auc. Area under the curve dr ashwin r linkedin slideshare. Bioavailability f is a measure of the systemic availability of a drug administered by a route other than iv. The fundamental principles of compartmental pharmacokinetics.
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