Pharmacokinetics and biopharmaceutics courses have been included in pharmacy curricula across the united states and in many other countries for the past several years. Biotransformation occurs in nearly all tissues, but the main site is the liver. Dose dependent pharmacokinetics involves a change in the rate process when the dose is changed, where as time dependent pharmacokinetics is a result of alteration in physiology or biochemistry in an organ in the body that influences drug disposition circadian rhythms in gastrointestinal ph can affect drug dissolution, and circadian rhythms in gastric emptying, motility. Dosedependent pharmacokinetics of itraconazole after intravenous. In each case the result is a smaller proportion of drug in bound form and more free drug in the plasma.
Clinical pharmacokinetics of phenytoin springerlink. An example of a drug that has nonlinear pharmacokinetics pk is erythropoietin or epo. Basic pharmacokinetics 2nd edition pdf free download preface. Pharmaceutical factors extrinsic factorsdrug related factors 1. Rats were housed in metabolic cages tecniplast, varese, italy supplied with filtered pathogenfree air and food samyang company, seoul, korea and water ad. Temporal changes in the rate process of a drug which can be cyclical over a constant periode. Introduction to pharmacokinetics nurse prescribing. 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. This phenomenon is thought to be due to adaptive resistance or through a down regulation of aminoglycoside transport into the bacteria through energy dependent transport processes. For these drugs drugs with nonlinear kinetics or dose dependent kinetics, the kinetic parameters, such as clearance, volume of distribution, and half life, may vary depending on the administered dose. Modeling of pharmacokinetics and pharmacodynamics with. The importance of nonlinear dosedependent pharmacokinetics in hazard assessment.
Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. All the basic concepts of pharmacokinetics pks are described, with an emphasis on understanding what. Pharmacokinetics made easy 1rpresents the complex subject of pharmacokinetics in a simple, easytounderstand manner, lending itself to a wide audience including medical practitioners, health professionals and students of pharmacology, medicine and nursing. It will explore the processes of absorption, distribution, metabolism and excretion to chart a drugs route from administration to elimination. Dec, 2012 phenytoin is a relatively insoluble weak acid, usually administered as the sodium salt. Module 1pharmacodynamics and pharmacokinetics flashcards. Phar 7633 chapter 21 nonlinear pharmacokinetic models scheme or diagram diagram 21. Nonlinear pharmacokinetics applied biopharmaceutics. Presentations ppt, key, pdf logging in or signing up. Relationship between pharmacokinetics and pharmacodynamics of.
For example, dabigatran pharmacokinetics is largely dependent on. Physical pharmacy, physical chemical principal in pharmaceutical science, indian edition, k m varghese, bombay, 366 powerpoint templates page 18. Analysis of urine data, intravenous infusion, pharmacokinetics of oral administration, multiple iv bolus dose administration, multiple oral dose administration, routes of excretion, metabolism, multicompartment pharmacokinetic models, nonlinear pharmacokinetic models. Concentrationdependent killing richard quintiliani, m. Nonlinear pharmacokinetics in other words, time or dose dependences in pharmacokinetic parameters can arise from factors associated with absorption, firstpass metabolism, binding, excretion and biotransformation. The extraction in the liver is simply the ratio of the hepatic clearance and the liver blood flow riegelman and rowland, 1973. Nonlinear kinetics is usually due to saturation occuring in one of the pharmacokinetic mechanisms. Noncompartmental pk analysis is highly dependent on estimation of total. The drug has a moderately large volume of distribution and is approximately 90% bound to plasma proteins. You may have heard about epo in the context of sports because it is a performance enhancing drug ped. Abstract the aim of the present study was to investigate the pharmacokinetic and pharmacodynamic characteristics of febuxostat following the administration of single and multiple oral doses under fasting conditions to healthy individuals. Test bank for pharmacology an introduction 6th edition by.
May 15, 2014 pharmacokinetics lecture notes janfeb 2014 2 absorption it is the movement of a drug from its site of administration into the central compartment and the extent to which this occurs. Pharmacokinetics, pharmacodynamics, and pharmacogenomics by simon w. Dose dependent pharmacokinetics 83 the absorption of drugs may be enhanced by binding to plasma proteins. Introduction to pharmacokinetics and pharmacodynamics ashp. For many drugs, the gastrointestinal absorption rate, but not the. Pharmacokinetics download free ebooks for students and. If anyone has an idea of downloading the winonlin software trial version or free download, please help me. The time dependency of the absorption rate constant was described using a sigmoidal emax model. Pharmacokinetics deals with the movement of a drug from its administration site to the place of its pharmacologic activity and its elimination from the body. Submit request what is very important to us is that you have all details about your textbook such as complete title, edition, author and isbn. The university paris diderot and inserm are the coowners of this library of functions version 3. Download fulltext pdf dosedependent pharmacokinetics of amphotericin b lipid complex in rabbits article pdf available in antimicrobial agents and chemotherapy 448. Previous chapters discussed linear pharmacokinetic models using simple. Clinically important displacement can be caused by bilirubin and.
Ppt pharmacokinetics calculations powerpoint presentation. Pharmacokinetics sometimes abbreviated as pk, is a branch of pharmacology dedicated to. Jan 22, 2014 contents of the powerpoint on non compartmental pharmacokinetics include. Drug binding many drugs will bind strongly to proteins in the blood or to food substances in the gut. In a drug with nonlinear kinetics, doubling the dose will double the concentration. A pkpd experiment consists of pharmacokinetic and pharmacodynamic measurements performed in a population of individuals. Phenytoin needs to be given twice or 3 times daily because it has a halflife of about 12 hours. Dosedependent pharmacokinetics 95 the hepatic clearance may be concentrationdependent according to michaelismenten kinetics, which implies that the extraction in the gi tract wall and the liver may. This article is from experimental and therapeutic medicine, volume 7. In one study of the effect of albumin concentration on total and free phenytoin concentrations, free fraction of phenytoin was inversely related to plasma albumin concentration in 10 critically ill trauma patients boucher 1988.
In the previously mentioned study of carbamazepine in rat valli et al. The chronic toxicity of chemicals is evaluated most frequently in animal species and these results subsequently applied to assessing exposure hazards to man. Time dependent pharmacokinetics involves an alteration in the biochemistry in an organ or physiological changes in patient. Combining pharmacokinetics pk and pharmacodynamics pd gives an overall picture of the drug response. Binding to plasma proteins will increase the rate of passive absorption by maintaining the concentration gradient of free drug. Pharmacokinetics, pharmacodynamics, and pharmacogenomics. These programs are not demos or trial versions, they do not expire, and they are free to use for educational, noncommercial use without any charge. Phar 7633 chapter 21 nonlinear pharmacokinetic models. D department of pharmaceutics kle university s college of pharmacy a free powerpoint ppt presentation displayed as a flash slide show on id.
Clinical pharmacokinetics and pharmacodynamics of propofol rug. Downloaded from the university of groningenumcg research database pure. Pharmacokinetics biotransformation of drugs typically reduces the lipophilicity, resulting in metabolites that are more likely to be excreted by the kidney, or discharged into the intestine. Compartmentfree modelling based on curve stripping does not suffer this. Select a pharmacokinetic model from a library, or create mechanismbased pkpd models using the interactive blockdiagram editor estimate model parameters using nonlinear regression or nlme methods explore system dynamics, using parameter sweeps and sensitivity analysis. Carbamazepine free fraction decreased by 50% from 10. Drugs may compete for binding with plasma proteins leading to interactions. Jaiswal, biopharmaceutics and pharmacokinetics, a treatise 305314. Thus, ibuprofenalthough very poorly solubleis very rapidly absorbed, perhaps because of its strong binding to albumin. The advantages and disadvantages of the described stable. The free aqueous concentration of propofol is thought to be reduced. Professor of clinical pharmacology, flinders university of south australia, adelaide.
The greater amount of free drug is able to produce a greater therapeutic effect and reduced drug dosages may be indicated in these cases. Download fulltext pdf pharmacokinetics of nacetylcysteine in man article pdf available in european journal of clinical pharmacology 312. Time dependent pharmacokinetics recent developments by rene h. Antibiotic kinetics for dos antibiotic kinetics for dos is a text based program which runs under msdos, windows 3. However, their use without a clear understanding of physiological parameters affecting the pk parameters and how different pk parameters are related to each other may result in erroneous interpretation of data. Sample chapter for basic pharmacokinetics 2nd edition. Basic pharmacokinetics sample chapter pharmaceutical press. Illustrative data are provided from tracer studies performed with a drug with dose. Bioavailability is dependent upon particle size and problems of generic inequivalence have therefore arisen, particularly in scandinavia. In pkpd it is assumed that the drug concentration is the driving force of the pharmacological e.
You may come across a phrase like the following and wonder what it means. Nonlinearities in absorption and bioavailability can cause increases in drug concentrations that are disproportionately high or low relative to the change in dose. Non linear pharmacokinetics pharmacokinetics enzyme. Basic pharmacokinetics 2nd edition pdf free medical books. Abstract pharmacokinetic pk software packages are widely used by scientists in different disciplines to estimate pk parameters. It is the time dependent change in the pharmacokinetic parameters. This article begins by examining the basic concepts of pharmacokinetics to allow the reader to improve their understanding of drug handling within the body. Introduction to pharmacokinetics and pharmacodynamics. Mathematical expressions of the pharmacokinetic and.
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