University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
The document summarizes various methods for screening peptic ulcer drugs, including both in vitro and in vivo models. In vitro methods include assays that measure inhibition of H+/K+-ATPase, while common in vivo models in rats include the pylorus ligation model, ethanol-induced gastric lesions, acetic acid-induced gastric ulcers, and cysteamine-induced duodenal ulcers. The pylorus ligation model involves ligating the pylorus of rats for 6 hours to induce ulcers, after which ulcer severity is scored. Several other chemical models use agents like ethanol, acetic acid, or cysteamine to directly damage the stomach lining of rats.
This document discusses linear and nonlinear pharmacokinetics. [1] Linear pharmacokinetics follow first-order kinetics where the rate of drug absorption, distribution, metabolism and excretion is proportional to dose. [2] Nonlinear pharmacokinetics occur when these processes become saturated at high doses due to limited enzyme or transporter capacity. [3] Michaelis-Menten kinetics are often used to model nonlinear processes and estimate parameters like Vmax and Km.
Detection, reporting and management of adverse eventsKatla Swapna
This document discusses adverse drug reactions (ADRs), including definitions, classifications, detection, reporting, and management. It notes that ADRs are a major clinical problem that can cause suffering and increased healthcare costs. It emphasizes the importance of monitoring and reporting ADRs to improve patient safety. Pharmacists can play an important role by monitoring high-risk patients and drugs, educating on ADR reporting, and assisting in the detection and assessment of ADRs. Timely reporting of ADRs is crucial to help prevent human suffering and unnecessary costs from drug-related injuries.
Bioavailability refers to the percentage of an administered drug dose that reaches systemic circulation in an unchanged form. It is calculated as the bioavailable dose divided by the administered dose. Absolute bioavailability compares bioavailability of a non-intravenous dose to an intravenous dose, while relative bioavailability compares bioavailability between different formulations of the same drug. Many factors can affect a drug's bioavailability including its physical properties, the dosage form, physiological factors like pH and transit time, and first-pass metabolism. Volume of distribution represents the hypothetical volume that the drug distributes into in the body and half-life is the time for a drug amount or concentration to reduce by half, which is affected by volume of distribution and clearance.
Bioavailability and bioequivalence studies are essential to ensure uniform quality, efficacy, and safety of pharmaceutical products. Bioavailability measures the rate and amount of drug that reaches systemic circulation, while bioequivalence demonstrates that generic and brand name products have comparable rates and extents of absorption. Well-designed pharmacokinetic studies are commonly used to assess bioequivalence by comparing AUC and Cmax of test and reference products. Factors like dosage form, solubility, transit time and metabolism can influence bioavailability, so studies may be necessary after manufacturing changes or for different routes of administration. Guidelines regulate bioequivalence testing to allow approval of lower-cost generic drugs while maintaining therapeutic equivalence.
Cancer is characterized by uncontrolled cell proliferation. Many factors can cause cancer, including external factors like chemicals and radiation, and internal factors like hormones and genetic mutations. While there are 92 approved anticancer drugs, effective therapies are still lacking for many types of cancer. New drugs are needed that are more selective for cancer cells to reduce side effects from long-term treatment. In vitro screening methods are used to identify potential drug candidates, including assays to test cell viability, proliferation, and morphology. Promising candidates then advance to in vivo testing using animal models of cancer like chemically-induced tumors in mice. The goal is to find drugs that can effectively treat cancer while avoiding side effects.
This document discusses compartment modeling in pharmacokinetics. It begins by defining a mathematical model and compartment model. Compartmental models divide the body into compartments and use first-order kinetics to describe the movement of drugs between compartments. Common compartment models include one-compartment open models for intravenous bolus, intravenous infusion, and extravascular administration. Determination of pharmacokinetic parameters like absorption rate, elimination rate constant, and half-life are also covered.
Circadian rhythms are biological processes that display an approximately 24-hour cycle. The document discusses the history and types of biological rhythms, focusing on circadian rhythms which are regulated by the suprachiasmatic nucleus in the brain. It describes how circadian rhythms influence many physiological functions and the absorption, distribution, metabolism, and elimination of drugs. Timed or chronotherapy aims to deliver drugs at times that synchronize with the body's natural rhythms to maximize efficacy and minimize side effects.
This document describes several animal models used to screen for potential antidepressant drugs, including the water wheel model, learned helplessness test, tail suspension test, amphetamine potentiation test, and muricidal behavior model. It explains the procedures and principles of each test, noting that some classical antidepressants reduce immobility time in tests like the water wheel and forced swim tests. However, these models have limitations and may not accurately model human depression or detect all effective antidepressants.
This document summarizes screening methods for evaluating potential anti-inflammatory drugs. It discusses the inflammatory response and various animal models used to test drug candidates, including carrageenan-induced paw edema, cotton pellet-induced granuloma, and UVB-induced erythema in guinea pigs. Several in vitro assays are also described, such as measuring COX inhibition and evaluating the ability of drugs to block mast cell degranulation and platelet-neutrophil adhesion. The goal of these screening methods is to effectively identify drug candidates that can target different phases and components of the inflammatory process.
Pharmacological screening of Anti-psychotic agentsAbin Joy
This document provides information on screening models used to evaluate potential antipsychotic drugs. It begins with an introduction to psychosis and classification of antipsychotic agents. It then describes several in vivo and in vitro models used for screening including tests measuring catalepsy in rodents, inhibition of amphetamine-induced stereotypy, and D2 receptor binding assays. The in vivo models assess behaviors relevant to antipsychotic effects while the in vitro assays measure binding to specific receptors like the D2 receptor that contribute to antipsychotic mechanisms of action.
This presentation summarizes key concepts regarding bioavailability and bioequivalence studies. It defines bioavailability as a measure of the rate and amount of drug reaching systemic circulation following administration of a dosage form. Absolute bioavailability compares intravenous and oral administration, while relative bioavailability compares oral formulations. The objectives of these studies are outlined. Methods of measuring bioavailability through pharmacokinetic methods like plasma level time studies and urinary excretion studies are described. Bioequivalence ensures two dosage forms reach systemic circulation at the same rate and extent. Study designs for in vivo and in vitro bioequivalence experiments are discussed, including completely randomized, randomized block, repeated measures, cross-over, and Latin square designs.
This document summarizes screening models for diuretic agents. It discusses various in vitro and in vivo models including isolated tubule preparation, carbonic anhydrase inhibition assay, patch clamp technique, Lipschitz test, saluretic activity in rats, stop flow technique, clearance method, and micropuncture technique. It provides details on the principles, procedures, and evaluations of these models for studying mechanisms and effects of diuretic agents. The models allow localization of sites of action and analysis of renal transport processes to evaluate diuretics and their carbonic anhydrase inhibiting or potassium sparing effects.
The document discusses nonlinear pharmacokinetics and chronopharmacokinetics. Nonlinear pharmacokinetics occurs when the body's absorption, distribution, metabolism, or excretion of a drug becomes saturated at higher doses. This can cause the rate of drug elimination to decrease. Examples of processes that can become saturated include drug metabolism and renal excretion. Circadian rhythms can also impact drug pharmacokinetics by influencing absorption, distribution, metabolism, and excretion over 24-hour periods. Accounting for these temporal changes can improve drug therapy for circadian phase-dependent diseases.
This document discusses linear and non-linear pharmacokinetics. Linear pharmacokinetics follows first-order kinetics where the rate of change in drug concentration depends only on the current concentration. In non-linear pharmacokinetics, the rate depends on carrier enzymes that can become saturated at high drug concentrations, causing the kinetics to follow mixed or zero-order processes and parameters to change with dose. Non-linearity can be caused by saturation of absorption, distribution, metabolism or excretion processes. The Michaelis-Menten equation describes non-linear kinetics and parameters. Km and Vmax can be estimated from plasma concentration data using Lineweaver-Burk, Eadie-Hofstee or Han
Dear Friends,
This is my 3rd presentation, which will help you to understand the depth knowledge of acute eye irritation/corrosion (OECD-405) study in rabbit.
This document appears to be 3 scanned pages from a mobile device application called CamScanner. The pages are blank except for a watermark indicating they were scanned with CamScanner. In summary, the document provides no substantive information due to being 3 blank scanned pages from a mobile scanning application.
This document discusses bioavailability and bioequivalence concepts including definitions, objectives of bioavailability studies, types of bioavailability studies, and methods of measuring bioavailability. It also covers bioequivalence experimental study designs including completely randomized, randomized block, repeated measures, and Latin square designs. In vitro dissolution studies and developing in vitro-in vivo correlations to help assess bioavailability without human studies are also summarized.
This document discusses pharmacokinetic models, which are mathematical models used to predict how drugs move through the body over time. It describes several types of pharmacokinetic models including compartment models that divide the body into hypothetical compartments and non-compartment models. Compartment models include one, two, and multi-compartment models. Pharmacokinetic models can also be classified based on elimination rate constants, compartment arrangement, and physiology. The document provides examples and diagrams of different pharmacokinetic models and discusses their applications in drug development and clinical practice.
Clinical pharmacology studies how medications act in the human body. It has several key areas of focus: pharmacodynamics examines the effects of drugs and their mechanisms of action; pharmacokinetics studies how the body absorbs, distributes, metabolizes and eliminates drugs. Pharmacogenetics explores genetic factors influencing individual responses to medications. Receptors play an important role in how drugs produce their effects, and drugs can act through different receptor types or mechanisms to produce their intended or side effects.
This document provides an overview of pharmacokinetics, including definitions, compartment models, non-compartment models, physiological models, and a one-compartment open model. Pharmacokinetics describes the absorption, distribution, metabolism, and excretion of drugs in the body. Compartmental models represent the body as a series of compartments and use rate constants to describe drug movement between compartments. A one-compartment open model can be used to model intravenous bolus administration, where drug is eliminated from the body via first-order kinetics.
The dose of propranolol administered intravenously is less than that administered orally because of first pass effect through the liver.
When a drug is administered orally, it is absorbed through the gastrointestinal tract and enters the portal circulation, which carries blood directly from the intestines to the liver. This exposes the drug to high concentrations of hepatic drug metabolizing enzymes before it reaches systemic circulation. Many drugs, including propranolol, are extensively metabolized in the liver during first pass. This reduces the amount of unchanged/active drug that reaches the systemic circulation compared to intravenous administration, which bypasses first pass metabolism. Therefore, a higher oral dose is needed to achieve the same systemic drug concentration as a lower intravenous dose.
Non-linear pharmacokinetics occurs when the rate of absorption, distribution, metabolism, or excretion of a drug depends on the dose administered. This can be due to saturation of enzymes involved in drug metabolism or transporters involved in absorption and excretion. According to the Michaelis-Menten equation, the rate of drug clearance will approach a maximum theoretical rate (Vmax) as the drug concentration increases, leading to non-linear kinetics. In linear kinetics, pharmacokinetic parameters are constant regardless of dose, while in non-linear kinetics they are dose-dependent.
Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure (medications for the sake of this article). This is closely related to but distinctly different from pharmacodynamics, which examines the drug's effect on the body more closely.
Michaelis-Menten kinetics is commonly used to describe non-linear pharmacokinetics when drug metabolism or elimination involves saturable enzyme systems. Non-linearity occurs when the capacity of the enzyme is exceeded, leading to saturation. This document discusses various causes and examples of non-linear pharmacokinetics, including saturation of absorption, distribution, metabolism and excretion processes. It also describes the two-compartment open model and how drug concentrations change in each compartment over time following intravenous bolus dosing.
The document discusses the applications of pharmacokinetics in new drug development, dosage form design, and novel drug delivery systems (NDDS). It covers key topics such as:
1) How pharmacokinetic principles can be applied to the design and development of new drugs, controlled release formulations, and the selection of appropriate routes of administration.
2) The important pharmacokinetic parameters used in characterization and the approaches used for dosage regimen design.
3) How pharmacokinetics can aid in formulation development, bioavailability/bioequivalence testing, and the development of various NDDS.
4) Considerations for dosing adjustments based on patient factors like obesity, age, hepatic or renal impairment
Pharmacokinetics of Drug_Pharmacology Course_Muhammad Kamal Hossain.pptxMuhammad Kamal Hossain
Pharmacokinetics is defined as the kinetics of drug absorption, distribution, metabolism and excretion (ADME) and their relationship with the pharmacological, therapeutic or toxicological response in man and animals.
Drug absorption from the gastrointestinal tract can be influenced by many factors. The drug must first disintegrate, dissolve, and permeate the gastrointestinal membranes before being absorbed into systemic circulation. The rate of absorption is determined by the slowest of these steps. Factors that can affect absorption include the drug's physicochemical properties, dosage form characteristics, and patient factors like gastrointestinal pH, transit time, and presence of food or enzymes. Understanding these biopharmaceutical factors is important for optimizing drug product design and therapeutic efficacy.
Pharmacokinetic models describe the absorption, distribution, and elimination of drugs in the body over time. There are three main types: empirical models simply describe the data, physiological models divide tissues into rapidly and slowly equilibrating groups based on blood flow, and compartment models represent tissues as "tanks" or compartments that communicate with each other. Compartment models use differential equations and can range from one to multiple compartments depending on the complexity needed to model the drug's behavior.
The document discusses concepts, events, and biological processes involved in drug targeting. It defines drug targeting as selectively delivering pharmacologically active drugs to identified targets in therapeutic concentrations while restricting access to non-targets to minimize toxicity. It describes various strategies for drug targeting including chemical modifications, carrier-mediated delivery, and active targeting. It also outlines biological processes involved like cellular uptake, transport across epithelial barriers, extravasation into tissues, and lymphatic uptake that influence drug distribution. The presentation emphasizes how targeted delivery can improve efficacy and safety of drug therapy especially for cancer.
This document discusses compartment modeling in pharmacokinetics. It defines a compartment as a group of tissues with similar blood flow and drug affinity. Compartment models represent the body as a series of compartments through which drugs move according to first-order kinetics. The two major types are mammillary models, with one central compartment connected to multiple peripheral compartments, and catenary models with compartments connected in series. Compartment models are simple and flexible, allowing prediction of drug concentration over time, though they lack full physiological relevance.
This document provides an overview of pharmacokinetics, specifically focusing on absorption. It defines pharmacokinetics as the study of what the body does to drugs. The four main processes are absorption, distribution, metabolism, and excretion (ADME). Absorption is defined as the passage of drugs through cell membranes to reach the site of action. The main mechanisms of absorption are described as simple diffusion, active transport, facilitated diffusion, and pinocytosis. Factors that influence absorption, such as drug properties and gastrointestinal factors, are also discussed.
This document provides an overview of pharmacokinetic models and parameters. It discusses one-compartment models for intravenous bolus and intravenous infusion administration. For intravenous bolus, the elimination rate constant, half-life, apparent volume of distribution, and clearance are defined. For intravenous infusion, the equations for drug concentration over time are presented. Compartmental models are used to mathematically describe drug behavior in the body and calculate pharmacokinetic parameters.
This document provides an introduction to the field of pharmacology. It defines pharmacology as the study of how drugs interact with living systems, including their effects, absorption, distribution, metabolism and excretion. The document outlines the key branches and concepts of pharmacology, including pharmacokinetics, pharmacodynamics, drug sources, nomenclature, administration routes, and factors affecting drug absorption.
This document provides an overview of basic concepts in biopharmaceutics including pharmacokinetic models and parameters. It discusses pharmacokinetic concepts like dosage regimen, pharmacokinetics, plasma drug concentration profiles, and pharmacokinetic parameters including Cmax, tmax, AUC, etc. It also covers pharmacokinetic models including compartment models, physiological models, and non-compartmental analysis. Specific compartment models like one-compartment open model for IV bolus and IV infusion are explained. Rate constants, orders of reactions, and processes like zero-order, first-order, and mixed-order kinetics are defined. Methods for estimating pharmacokinetic parameters from plasma concentration-time data are also summarized.
Similar to Concept of non linear and linear pharmacokinetic model (20)
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with "Quality control of packaging materials."
Thank you for reading.
we hope it was helpful to you.
UIPS,PU team
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with "Aseptic requirements for parenteral products".
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Hope it was of help to you.
UIPS,PU team
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the quality control tests of parenteral as referred in the pharmacopoeia.
Thank you for reading. Hope it was of help to you.
UIPS,PU team
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with qualifications of HPLC which is the " High Performance Liquid Chromatography".
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UIPS,PU team
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with basics impurity profiling and degradent characterization.
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Hope it was of help to you.
UIPS,PU team
This document provides information about tablets as a drug delivery system. It defines tablets and describes their key components and manufacturing process. Tablets consist of active pharmaceutical ingredients and excipients that control release and aid manufacturing. Excipients include fillers, disintegrants, binders, lubricants and others. Tableting involves powder compression in a die and punch press. Tablets offer benefits like precision dosing but some drugs are not suitable. Quality is ensured through testing dissolution and other properties.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the types of parenteral formulation including the types of parenteral route for administration along withcomponents of parenteral formulation.
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UIPS,PU team
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the 21 code of federal regulation Part 11.
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UIPS,PU team
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the concept of Diphtheria vaccine.
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UIPS,PU team
This document provides information about various vitamins. It discusses 13 vitamins - thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folic acid (B9), cyanocobalamin (B12), ascorbic acid (C), retinol (A), ergocalciferol (D), tocopherol (E), and phylloquinone (K). For each vitamin, it mentions the chemical name, sources, functions, deficiency symptoms, absorption and any relevant chemistry. The document provides details on the roles of these vitamins
The document discusses various types of containers used for pharmaceutical products, including glass and plastic containers. It provides details on different types of glass containers based on their composition, such as lime soda glass, borosilicate glass, and neutral glass. It also discusses plastic containers such as thermoplastics and thermosettings. The document then covers various types of injection containers, including single dose small volume containers like ampoules and cartridges, and single dose large volume containers like transfusion bottles. It also discusses the differences between single dose and multiple dose containers.
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Westgard's rules and LJ (Levey Jennings) Charts.Reenaz Shaik
Quality Control is a process used to monitor and evaluate the analytical process that produces patients results. Planning, documenting and agreeing on a set of guidelines ensures quality.
TEST BANK For Katzung's Basic and Clinical Pharmacology, 16th Edition By {Tod...rightmanforbloodline
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Why Does Seminal Vesiculitis Causes Jelly-like Sperm.pptxAmandaChou9
Seminal vesiculitis can cause jelly-like sperm. Fortunately, herbal medicine Diuretic and Anti-inflammatory Pill can eliminate symptoms and cure the disease.
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, drug repurposing has emerged as a promising strategy for the treatment of parasitic diseases. Drug repurposing, or drug repositioning, involves identifying new therapeutic uses for existing drugs. This approach leverages the known safety profiles, established manufacturing processes, and previously conducted clinical trials of existing drugs, thereby significantly reducing the time and cost associated with bringing new treatments to market.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the types of hypoxia.
Learning objectives:
1. Define hypoxia
2. Describe the causes and features of different types of hypoxia
3. Define cyanosis
4. Enumerate the causes of cyanosis
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 35, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Central and Peripheral Cyanosis - https://www.ncbi.nlm.nih.gov/books/NBK559167/
Descoperă Bucuria Vieții Sănătoase cu Jurnalul Fericirii Life Care - Iulie 2024!
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Pe parcursul a cateva de pagini pline de informații utile și inspirație, vei descoperi:
Sfaturi practice pentru o alimentație sănătoasă:
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vaginal thrush presentation by Dr. Rewas AliRewAs ALI
in these slides you know what is vaginal thrush, symptoms, and treatments with special population(pregnancy and lactation). you can see the explanation in my youtube channel in this link below:
https://youtu.be/ov5WqVwdHkE?si=iaF5MHC9Vv_6udzR
vaginal thrush is one of the most common gynecological complication that can be treated easily if diagnosed in a correct way.
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POTENTIAL TARGET DISEASES FOR GENE THERAPY SOURAV.pptxsouravpaul769171
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- Video recording of this lecture in Arabic language: https://youtu.be/kbDs1uaeyyo
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- Link to NephroTube website: www.NephroTube.com
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Welcome to the third issue of the second volume of NutriConnect, a bi-monthly newsletter brought to you by the Makerere University Human Nutrition Students Association. This edition focuses on the critical link between nutrition and mental health, exploring how what we eat impacts our mood, cognitive function, and overall mental well-being. Join us as we delve into the latest research, practical tips, and inspiring stories to help you nourish both your body and mind.
Concept of non linear and linear pharmacokinetic model
1. CONCEPT OF LINEAR &
NONLINEAR COMPARTMENT
MODELS
Submitted by:-
Nitin Rawat
M.Pharm (Pharmacology)
Submitted to:-
Prof. Anil Kumar
Professor of Pharmacology
UINVERSITY INSTITUTE OF PHARMACETICAL SCIENCES,PANJAB UNIVERSITY CHANDIGARH
2. CONTENT
• Introduction to pharmacokinetics
• Introduction to pharmacokinetic models
• Approaches of pharmacokinetic models
Model approach
• Compartment model
• Physiological model
• Distributed parameter model
Non-model approach
• Non-linear pharmacokinetics
• Comparisons between linear and non linear pharmacokinetics
3. PHRMACOKINETICS
Pharmacokinetics is defined as the kinetics of drug absorption, distribution,
metabolism and excretion (KADME) and their relationship with the
pharmacological, therapeutic or toxicological response in man and animals.
4. There are two aspects of pharmacokinetic studies –
1. Theoretical aspect – which involves development of pharmacokinetic
models to predict drug disposition after its administration. Statistical methods
are commonly applied to interpret data and assess various parameters.
2. Experimental aspect – which involves development of biological sampling
techniques, analytical methods for measurement of drug (and metabolites)
concentration in biological samples and data collection and evaluation.
Use of pharmacokinetic principles in optimizing the drug dosage for
individual patient in order to achieving maximum therapeutic utility is
called as clinical pharmacokinetics.
5. • Models are used to describe changes in drug concentration in the body with time.
• Model is a hypothesis that employs mathematical terms to concisely describe quantitative
relationships of drug(s)(w.r.t time) throughout the body and compute meaningful
pharmacokinetic parameters.
• Applications of Pharmacokinetic Models
• Characterizing the behavior of drugs in patients.
• Predicting the concentration of drug in various body fluids with any dosage regimen.
• Calculating the optimum dosage regimen for individual patients.
• Evaluating the risk of toxicity with certain dosage regimens.
• Estimating the possibility of drug and/or metabolite(s) accumulation in the body.
• Determining the influence of altered physiology/disease state on drug ADME.
• Explaining drug interactions.
PHARMACOKINETIC MODELS
7. Compartmental Models
• Compartment is not a real physiologic or anatomic region but a fictitious or virtual one and
considered as a tissue or group of tissues that have similar drug distribution characteristics
(similar blood flow and affinity).
• It is the traditional and commonly used approach to pharmacokinetic characterization of a drug.
These models simply interpolate the experimental data and allow an empirical formula to estimate
the drug concentration with time.
Assumptions
• Compartment is not a real physiologic or anatomic region but a fictitious or virtual one and
considered as a tissue or group of tissues that have similar drug distribution characteristics
(similar blood flow and affinity).
• The body is represented as a series of compartments arranged either in series or parallel to each
other, that communicate reversibly with each other.
• Within each compartment, the drug is considered to be rapidly and uniformly distributed i.e. the
compartment is well-stirred.
8. Types of compartmental models
• Compartment models are divided into two categories
• Depending upon arrangement of compartments
Mammillary model
Catenary model.
• Depending upon number of compartment assumed
One-compartment or one-compartment open model
Two compartment
Multiple compartment
9. Mammillary model
Central compartment (comprises of plasma and highly perfused tissues such as lungs, liver,
kidneys) joined parallel to the peripheral compartment(comprises of less perfused organ) like
connection of satellites to a planet.
Catenary model
Compartments are joined to one another in a series like compartments of a train. This is however
not observable physiologically/anatomically as the various organs are directly linked to the
blood compartment.
10. One-compartment open model
Body is considered as a single, kinetically
homogeneous unit that has no barriers to the
movement of drug
Open indicates that the input (availability) and
output (elimination) are unidirectional and that
the drug can be eliminated from the body.
11. One-compartment open model, i.v. bolus administration.
One-compartment open model, continuous i.v. infusion.
One-compartment open model, e.v. administration, zero-order
absorption
One-compartment open model, e.v. administration, first-order
absorption
Types One-compartment open model
12. TWO-COMPARTMENT OPEN MODEL
body tissues are broadly classified into 2 categories –
Central Compartment or Compartment 1
Comprising of blood and highly perfused tissues like liver, lungs,
kidneys, etc. that equilibrate with the drug rapidly.
Elimination usually occurs from this compartment.
Peripheral or Tissue Compartment or Compartment 2
Comprising of poorly perfused and slow equilibrating tissues such as
muscles, skin, adipose, etc. and considered as a hybrid of several functional physiologic units.
Classification of a particular tissue, for example brain, into central or peripheral compartment depends upon the
physicochemical properties of the drug.
Depending upon the compartment from which the drug is eliminated, the two-compartment model can be categorized into
3 types:
1.Two-compartment model with elimination from central compartment.
2.Two-compartment model with elimination from peripheral compartment.
3.Two-compartment model with elimination from both the compartments.
13. Also known as Physiological based pharmacokinetic model.
• They are drawn on the basis of known anatomic and physiological data and thus present a
more realistic picture of drug disposition in various organs and tissues.
Two types
• Perfusion rate-limited models
lipophilic drugs
• Diffusion-limited models
hydrophilic drugs
Physiological models
14. Distributed Parameter Model
• Useful for assessing regional differences in drug concentrations in tumours
or necrotic tissues.
• It take into account –
Variations in blood flow to an organ, and
Variations in drug diffusion in an organ.
15. Nonlinear Pharmacokinetics
In some cases, the rate process of a drug’s ADME are dependent upon carrier or enzymes
that are substrate-specific, have definite capacities, and susceptible to saturation at high drug
concentration. In such cases, an essentially first-order kinetics transform into a mixture of
first-order and zero-order rate processes and the pharmacokinetic parameters change with
the size of the administered dose. The pharmacokinetics of such drugs are said to be dose-
dependent. Other terms synonymous with it are mixed-order, nonlinear and capacity-
limited kinetics.
Drugs exhibiting such a kinetic profile are sources of variability in pharmacological
response.
16. CAUSES OF NONLINEARITY
Nonlinearity in drug absorption can arise from 3 important sources –
1. When absorption is solubility or dissolution rate-limited e.g. griseofulvin. At higher
doses, a saturated solution of the drug is formed in the GIT or at any other extravascular
site and the rate of absorption attains a constant value.
2. When absorption involves carrier-mediated transport systems e.g. absorption of
riboflavin, ascorbic acid, cyanocobalamin, etc. Saturation of the transport system at higher
doses of these vitamins results in nonlinearity.
3. When presystemic gut wall or hepatic metabolism attains saturation e.g. propranolol,
hydralazine and verapamil. Saturation of presystemic metabolism of these drugs at high
doses leads to increased bioavailability.
1. Drug Absorption
17. Nonlinearity in distribution of drugs administered at high doses may be due to –
1. Saturation of binding sites on plasma proteins e.g. phenylbutazone and naproxen. There is
a finite number of binding sites for a particular drug on plasma proteins and, theoretically, as
the concentration is raised, so too is the fraction unbound.
2. Saturation of tissue binding sites e.g. thiopental and fentanyl. With large single bolus doses
or multiple dosing, saturation of tissue storage sites can occur.
Drug Distribution
18. The nonlinear kinetics of most clinical importance is capacity-limited metabolism since small
changes in dose administered can produce large variations in plasma concentration at steady-
state. It is a major source of large intersubject variability in pharmacological response.
Two important causes of nonlinearity in metabolism are –
1. Capacity-limited metabolism due to enzyme and/or cofactor saturation. Typical examples
include phenytoin, alcohol, theophylline, etc.
2. Enzyme induction e.g. carbamazepine, where a decrease in peak plasma concentration has
been observed on repetitive administration over a period of time. Autoinduction characterized
in this case is also dose-dependent. Thus, enzyme induction is a common cause of both dose-
and time-dependent kinetics.
Drug Metabolism
19. The two active processes in renal excretion of a drug that are saturable are –
1. Active tubular secretion e.g. penicillin G. After saturation of the carrier system, a decrease
in renal clearance occurs.
2. Active tubular reabsorption e.g. water soluble vitamins and glucose. After saturation of the
carrier system, an increase in renal clearance occurs.
Drug Excretion
20. MICHAELIS MENTEN EQUATION
The kinetics of capacity-limited or saturable processes is best described by Michaelis- Menten equation:
−
𝑑𝑐
𝑑𝑡
=
𝑣 𝑚𝑎𝑥 𝐶
𝐾𝑚 + 𝐶
–dC/dt = rate of decline of drug concentration with time
Vmax = theoretical maximum rate of the process
Km = Michaelis constant
Three situations can now be considered depending upon the values of Km and C:
1. When Km = C
−
𝑑𝐶
𝑑𝑡
=
𝑉 𝑚𝑎𝑥
2
2. When Km >> C
Here, Km + C = Km
−
𝑑𝑐
𝑑𝑡
=
𝑣 𝑚𝑎𝑥 𝐶
𝐾𝑚
means that the drug concentration in the body that results from usual dosage regimens of most drugs is
well below the Km of the elimination process with certain exceptions such as phenytoin and alcohol.
3. When Km << C
Here, Km + C = C −
𝑑𝑐
𝑑𝑡
= 𝑉𝑚𝑎𝑥