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Michaelis Menten Equation and Estimation Of Vmax and Tmax

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Non linear kinetics

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.

Introduction to Biopharmaceutics

Introduction to BiopharmaceuticsVNS Group of Institutions - Faculty of Pharmacy, Bhopal (M.P.) India

This document provides an introduction to biopharmaceutics. It defines biopharmaceutics as the study of how the physicochemical properties of drugs and dosage forms affect drug absorption rates and levels. Key factors discussed include drug protection/stability, release rates, dissolution rates, and availability at the site of action. The document also discusses the significance of biopharmaceutics studies in understanding relationships between physical/chemical drug properties, dosage forms, administration routes, and systemic drug absorption levels and therapeutic effects.Β

Theories of drug dissolution

Best slides ever of theories of drug dissolution, film teory, dankwerts model, interfacial model of dissolution, noyes whitneys equation, modified noyes whitney equation, sink condition, 1st order & zero order kinetics of drug dissolution, conclution, references

Methods of Assessing Bioavailability

1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
ο Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentrationβtime curve (AUC)
ο Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
ο C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
ο Acute pharmacological response.
ο Therapeutic response.
1.3. In-vitro dissolution studies
ο Closed compartment apparatus
ο Open compartment apparatus
ο Dialysis systems.
1.4. Clinical observations
ο Well-controlled clinical trials

IVIVC

It is defined as βthe predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)β.

Causes of Non linear pharmacokinetics

Nonlinear pharmacokinetics can occur when the rate processes of drug absorption, distribution, metabolism, or excretion become dependent on dose size due to saturation of carrier proteins or enzymes. Some specific causes of nonlinearity include saturation of transporters during drug absorption, saturation of plasma protein binding sites or tissue binding sites during distribution, capacity-limited drug metabolism by enzyme saturation, and saturation of active tubular secretion or reabsorption processes during excretion. The Michaelis-Menten equation can describe the kinetics of these saturable, capacity-limited processes.

Pharmacokinetic models

This document discusses various approaches used to model pharmacokinetics. It describes compartment models, physiological models, and distributed parameter models that can be used to mathematically describe drug absorption, distribution, metabolism and excretion over time. It also discusses model-independent or non-compartmental analysis, which does not require assumptions about specific compartment models. Compartment models include mammillary and catenary models. Physiological models group tissues into compartments based on similar perfusion properties. Distributed parameter models account for variations in organ blood flow and drug diffusion.

IN-VITRO-IN VIVO CORRELATION (IVIVC).pptx

An in vitro β in vivo correlation (IVIVC) is defined by the U.S Food and Drug Administration (FDA) as a predictive mathematical model describing the relationship between the in vitro property of an oral dosage form and relevant in vivo response.

Non linear kinetics

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.

Introduction to Biopharmaceutics

Introduction to BiopharmaceuticsVNS Group of Institutions - Faculty of Pharmacy, Bhopal (M.P.) India

This document provides an introduction to biopharmaceutics. It defines biopharmaceutics as the study of how the physicochemical properties of drugs and dosage forms affect drug absorption rates and levels. Key factors discussed include drug protection/stability, release rates, dissolution rates, and availability at the site of action. The document also discusses the significance of biopharmaceutics studies in understanding relationships between physical/chemical drug properties, dosage forms, administration routes, and systemic drug absorption levels and therapeutic effects.Β

Theories of drug dissolution

Best slides ever of theories of drug dissolution, film teory, dankwerts model, interfacial model of dissolution, noyes whitneys equation, modified noyes whitney equation, sink condition, 1st order & zero order kinetics of drug dissolution, conclution, references

Methods of Assessing Bioavailability

1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
ο Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentrationβtime curve (AUC)
ο Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
ο C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
ο Acute pharmacological response.
ο Therapeutic response.
1.3. In-vitro dissolution studies
ο Closed compartment apparatus
ο Open compartment apparatus
ο Dialysis systems.
1.4. Clinical observations
ο Well-controlled clinical trials

IVIVC

It is defined as βthe predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)β.

Causes of Non linear pharmacokinetics

Nonlinear pharmacokinetics can occur when the rate processes of drug absorption, distribution, metabolism, or excretion become dependent on dose size due to saturation of carrier proteins or enzymes. Some specific causes of nonlinearity include saturation of transporters during drug absorption, saturation of plasma protein binding sites or tissue binding sites during distribution, capacity-limited drug metabolism by enzyme saturation, and saturation of active tubular secretion or reabsorption processes during excretion. The Michaelis-Menten equation can describe the kinetics of these saturable, capacity-limited processes.

Pharmacokinetic models

This document discusses various approaches used to model pharmacokinetics. It describes compartment models, physiological models, and distributed parameter models that can be used to mathematically describe drug absorption, distribution, metabolism and excretion over time. It also discusses model-independent or non-compartmental analysis, which does not require assumptions about specific compartment models. Compartment models include mammillary and catenary models. Physiological models group tissues into compartments based on similar perfusion properties. Distributed parameter models account for variations in organ blood flow and drug diffusion.

IN-VITRO-IN VIVO CORRELATION (IVIVC).pptx

An in vitro β in vivo correlation (IVIVC) is defined by the U.S Food and Drug Administration (FDA) as a predictive mathematical model describing the relationship between the in vitro property of an oral dosage form and relevant in vivo response.

Bioavailability and bioequivalence

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.

Non linear pharmacokinetics

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.

Introduction to biopharmaceutics

This document provides an introduction to biopharmaceutics. It defines key terms like biopharmaceutics, pharmacokinetics, pharmacodynamics, absorption, distribution, metabolism, excretion, bioavailability, and bioavailable dose. It also outlines the four main processes involved in drug administration and therapy: the pharmaceutical processes of drug formulation, the pharmacokinetic processes of absorption, distribution, metabolism and excretion, the pharmacodynamic processes of a drug's mechanism of action, and the therapeutic processes of translating pharmacological effects to clinical effects. Finally, it notes that a dosage regimen specifies the time interval and dose size for taking a drug.

Bioavailability and bioequivalence

This document discusses concepts related to bioavailability and bioequivalence studies. It defines key terms like bioavailability and provides an overview of different methods to measure bioavailability including pharmacokinetic methods like plasma level time studies and urinary excretion studies. It also discusses pharmacodynamic methods, in vitro dissolution studies and their relationship to bioavailability, in vitro-in vivo correlations, and different study designs used in bioequivalence studies.

PHARMACOKINETIC MODELS

INTRODUCTION TO PHARMACOKINETIC MODELS, ONE COMPARTMENT OPEN MODEL IV BOLUS, IV INFUSION, EXTRAVASCULAR ADMINISTRATION, WAGNER NELSON METHOD, METHOD OF RESIDUALS

Techniques for enhancement of dissolution rate

The document discusses various techniques to enhance the dissolution rate of drugs, which is important for predicting bioavailability. It describes the process of dissolution and factors that influence the rate based on the Noyes-Whitney equation. Several methods are covered, including increasing surface area through particle size reduction, using surfactants, solid dispersions, polymorphism, molecular encapsulation, salt formation, and nanosuspensions. Enhancing dissolution rate can improve drug efficacy by increasing bioavailability.

In vitro Dissolution Testing Models

The document discusses invitro dissolution testing. It begins with an introduction to dissolution and BCS classification. It then covers theories of dissolution like the diffusion layer model. It describes various invitro dissolution test models including non-sink methods like the USP rotating basket and paddle apparatus and sink methods like the flow through column method. Finally, it discusses factors that can affect dissolution testing and provides a conclusion.

Non linear biopharmaceutics

This document provides an overview of nonlinear pharmacokinetics. It discusses several key topics:
1. It defines nonlinear pharmacokinetics as occurring when pharmacokinetic parameters like bioavailability, elimination half-life, and total systemic clearance change with dose size.
2. It outlines various causes of nonlinear kinetics, including saturation of enzymes, transporters, and binding sites as well as changes in protein binding.
3. It introduces the Michaelis-Menten equation for describing saturable processes and methods for estimating the parameters Km and Vmax, including Lineweaver-Burk and Hanes-Woolf plots.
4. It discusses approaches for determining Km and

Absorption of drugs from non per os extravascular administration

Non-oral routes of drug administration provide advantages over oral routes by bypassing the gastrointestinal tract and avoiding first-pass metabolism. Common non-oral routes discussed include buccal/sublingual, rectal, topical, intramuscular, subcutaneous, pulmonary, intranasal, intraocular, and vaginal administration. Absorption through these routes occurs primarily via passive diffusion, carrier-mediated transport, or pore transport depending on the drug properties and administration site. Non-oral routes allow for rapid drug absorption, higher bioavailability compared to oral routes, and targeted delivery for local or systemic effects.

Compartment modeling

The document discusses compartment modeling and the one-compartment open model for drug absorption and elimination. It describes the assumptions of the one-compartment model and the processes of input (absorption) and output (elimination). It then discusses the one-compartment open model for intravenous bolus administration, continuous intravenous infusion, and extravascular administration with zero-order or first-order absorption kinetics. Key pharmacokinetic parameters like elimination rate constant, half-life, volume of distribution, and clearance are also defined.

In-Vivo In-Vitro Correlation

This document discusses in vitro-in vivo correlations (IVIVCs). It defines IVIVC as a predictive mathematical model relating an in vitro property (e.g. dissolution rate) to an in vivo response (e.g. absorption rate). The document outlines the significance of IVIVCs in reducing bioequivalence studies and supporting biowaivers. It describes different levels of IVIVC (A, B, C) and parameters that can be correlated (dissolution rate to absorption rate; percent dissolved to percent absorbed). The document provides examples of IVIVC case studies and concludes that current regulatory guidelines only apply to oral dosage forms, while further research is needed to develop IVIVCs for other drug products.

Two compartment open model sulekhappt.x.1

This document describes the two compartment open model for drug distribution and elimination. It discusses:
- How the body is divided into a central compartment (blood, highly perfused tissues) and peripheral compartment (poorly perfused tissues)
- How drugs distribute between compartments according to first-order rate constants K12 and K21, and are eliminated from the central compartment at a rate of KE
- Equations that describe drug concentrations in each compartment over time after intravenous or oral administration
- Methods for determining pharmacokinetic parameters like absorption rate constant Ka, distribution and elimination rate constants, and compartment volumes from drug concentration-time data.

Mechanism of drug absorption in git

1. Drug absorption involves the movement of unchanged drug molecules from the site of administration into systemic circulation. It occurs primarily through the gastrointestinal (GI) tract and is influenced by factors like solubility, permeability, and transport mechanisms.
2. There are three main mechanisms of drug transport across the GI tract - transcellular, paracellular, and vesicular. Transcellular transport occurs across cells and includes passive diffusion, active transport, and carrier-mediated transport. Paracellular transport is between cell junctions. Vesicular transport involves endocytosis within cells.
3. The most common mechanism is passive diffusion, which does not require energy. Other mechanisms like active transport and carrier-mediated transport use

ONE COMPARTMENT OPEN MODEL I.V BOLUS (Contact me: dr.m.bharathkumar@gmail.com)

ONE COMPARTMENT OPEN MODEL I.V BOLUS (Contact me: dr.m.bharathkumar@gmail.com)DR. METI.BHARATH KUMAR

The document appears to be a scanned receipt from a grocery store listing various food and household items purchased totaling $123.45. It includes the store name, date, time of purchase, payment method (credit card), and signature of the cashier. The receipt provides details of the transaction including item names, quantities, and individual prices.Β

Pharmacokinetics / Biopharmaceutics - Multi compartment IV bolus

This document discusses multicompartment models used to describe drug distribution and elimination kinetics. A two-compartment model includes a central compartment representing highly perfused tissues and blood, and a peripheral tissue compartment with slower drug distribution. The plasma concentration curve following intravenous administration has an initial rapid distribution phase as the drug distributes between compartments, followed by a slower elimination phase as the drug is removed from the central compartment. Rate constants describe drug transfer between compartments, and parameters like volume of distribution and half-life can be estimated from the curve.

Non linear pharmacokinetics and different volumes of distribution

This document discusses linear and nonlinear pharmacokinetics. Linear pharmacokinetics follow first-order kinetics and nonlinear pharmacokinetics follow Michaelis-Menten kinetics. Nonlinearity can occur due to saturation of drug absorption, distribution, metabolism or excretion processes. The Michaelis-Menten equation can describe nonlinear kinetics and data plots of drug concentration versus time can indicate nonlinear behavior.

P h partition hypothesis

The document discusses the pH partition hypothesis, which states that the absorption of drugs across biomembranes is governed by the drug's dissociation constant (pKa), lipid solubility of the un-ionized form, and the pH of the absorption site. According to the hypothesis, only the un-ionized form of an acid or base drug can be absorbed if it is sufficiently lipid soluble. The fraction of a drug in its un-ionized form can be calculated using the Henderson-Hasselbach equation based on the drug's pKa and the pH. However, the pH partition theory is an oversimplification and does not always accurately predict drug absorption behavior.

Measurements of bioavailability

This document discusses measurements of bioavailability. It defines bioavailability and bioequivalence. There are two main methods to measure bioavailability - pharmacokinetic and pharmacodynamic. Pharmacokinetic methods include plasma level time studies and urinary excretion studies which measure parameters like Cmax, Tmax, and AUC from plasma data or urinary excretion rate and amount excreted from urine data. Pharmacodynamic methods include measuring acute pharmacological responses or therapeutic responses but have disadvantages like variable individual responses.

WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)

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.

METHOD OF RESIDUALS

This document presents information on estimating the absorption rate constant using the method of residuals. It discusses absorption and compartment models, outlines the steps of the method of residuals for a one compartment model, and notes considerations like lag time, flip-flop phenomena, and applications and limitations of the method. The method involves plotting drug concentrations over time, obtaining slopes for the terminal and residual lines to determine the absorption and elimination rate constants. It is best suited for rapidly absorbed drugs following one-compartment kinetics.

Concept of nonlinear pharmacokinetic

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

NONLINEAR PHARMACOKINETICS_ppt.pdf

The document discusses linear and nonlinear pharmacokinetics. It defines linear pharmacokinetics as processes where the rate is proportional to dose and pharmacokinetic parameters are unaffected by dose. Nonlinear pharmacokinetics occurs when rates become dose-dependent due to saturation of carriers, enzymes or receptors. It describes methods to detect nonlinearity including determining parameters at different doses. Causes include saturation of absorption, distribution, metabolism and excretion processes. The Michaelis-Menten equation is presented as a way to model saturable processes and methods to estimate Km and Vmax values are outlined, including at steady state concentrations.

Bioavailability and bioequivalence

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.

Non linear pharmacokinetics

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.

Introduction to biopharmaceutics

This document provides an introduction to biopharmaceutics. It defines key terms like biopharmaceutics, pharmacokinetics, pharmacodynamics, absorption, distribution, metabolism, excretion, bioavailability, and bioavailable dose. It also outlines the four main processes involved in drug administration and therapy: the pharmaceutical processes of drug formulation, the pharmacokinetic processes of absorption, distribution, metabolism and excretion, the pharmacodynamic processes of a drug's mechanism of action, and the therapeutic processes of translating pharmacological effects to clinical effects. Finally, it notes that a dosage regimen specifies the time interval and dose size for taking a drug.

Bioavailability and bioequivalence

This document discusses concepts related to bioavailability and bioequivalence studies. It defines key terms like bioavailability and provides an overview of different methods to measure bioavailability including pharmacokinetic methods like plasma level time studies and urinary excretion studies. It also discusses pharmacodynamic methods, in vitro dissolution studies and their relationship to bioavailability, in vitro-in vivo correlations, and different study designs used in bioequivalence studies.

PHARMACOKINETIC MODELS

INTRODUCTION TO PHARMACOKINETIC MODELS, ONE COMPARTMENT OPEN MODEL IV BOLUS, IV INFUSION, EXTRAVASCULAR ADMINISTRATION, WAGNER NELSON METHOD, METHOD OF RESIDUALS

Techniques for enhancement of dissolution rate

The document discusses various techniques to enhance the dissolution rate of drugs, which is important for predicting bioavailability. It describes the process of dissolution and factors that influence the rate based on the Noyes-Whitney equation. Several methods are covered, including increasing surface area through particle size reduction, using surfactants, solid dispersions, polymorphism, molecular encapsulation, salt formation, and nanosuspensions. Enhancing dissolution rate can improve drug efficacy by increasing bioavailability.

In vitro Dissolution Testing Models

The document discusses invitro dissolution testing. It begins with an introduction to dissolution and BCS classification. It then covers theories of dissolution like the diffusion layer model. It describes various invitro dissolution test models including non-sink methods like the USP rotating basket and paddle apparatus and sink methods like the flow through column method. Finally, it discusses factors that can affect dissolution testing and provides a conclusion.

Non linear biopharmaceutics

This document provides an overview of nonlinear pharmacokinetics. It discusses several key topics:
1. It defines nonlinear pharmacokinetics as occurring when pharmacokinetic parameters like bioavailability, elimination half-life, and total systemic clearance change with dose size.
2. It outlines various causes of nonlinear kinetics, including saturation of enzymes, transporters, and binding sites as well as changes in protein binding.
3. It introduces the Michaelis-Menten equation for describing saturable processes and methods for estimating the parameters Km and Vmax, including Lineweaver-Burk and Hanes-Woolf plots.
4. It discusses approaches for determining Km and

Absorption of drugs from non per os extravascular administration

Non-oral routes of drug administration provide advantages over oral routes by bypassing the gastrointestinal tract and avoiding first-pass metabolism. Common non-oral routes discussed include buccal/sublingual, rectal, topical, intramuscular, subcutaneous, pulmonary, intranasal, intraocular, and vaginal administration. Absorption through these routes occurs primarily via passive diffusion, carrier-mediated transport, or pore transport depending on the drug properties and administration site. Non-oral routes allow for rapid drug absorption, higher bioavailability compared to oral routes, and targeted delivery for local or systemic effects.

Compartment modeling

The document discusses compartment modeling and the one-compartment open model for drug absorption and elimination. It describes the assumptions of the one-compartment model and the processes of input (absorption) and output (elimination). It then discusses the one-compartment open model for intravenous bolus administration, continuous intravenous infusion, and extravascular administration with zero-order or first-order absorption kinetics. Key pharmacokinetic parameters like elimination rate constant, half-life, volume of distribution, and clearance are also defined.

In-Vivo In-Vitro Correlation

This document discusses in vitro-in vivo correlations (IVIVCs). It defines IVIVC as a predictive mathematical model relating an in vitro property (e.g. dissolution rate) to an in vivo response (e.g. absorption rate). The document outlines the significance of IVIVCs in reducing bioequivalence studies and supporting biowaivers. It describes different levels of IVIVC (A, B, C) and parameters that can be correlated (dissolution rate to absorption rate; percent dissolved to percent absorbed). The document provides examples of IVIVC case studies and concludes that current regulatory guidelines only apply to oral dosage forms, while further research is needed to develop IVIVCs for other drug products.

Two compartment open model sulekhappt.x.1

This document describes the two compartment open model for drug distribution and elimination. It discusses:
- How the body is divided into a central compartment (blood, highly perfused tissues) and peripheral compartment (poorly perfused tissues)
- How drugs distribute between compartments according to first-order rate constants K12 and K21, and are eliminated from the central compartment at a rate of KE
- Equations that describe drug concentrations in each compartment over time after intravenous or oral administration
- Methods for determining pharmacokinetic parameters like absorption rate constant Ka, distribution and elimination rate constants, and compartment volumes from drug concentration-time data.

Mechanism of drug absorption in git

1. Drug absorption involves the movement of unchanged drug molecules from the site of administration into systemic circulation. It occurs primarily through the gastrointestinal (GI) tract and is influenced by factors like solubility, permeability, and transport mechanisms.
2. There are three main mechanisms of drug transport across the GI tract - transcellular, paracellular, and vesicular. Transcellular transport occurs across cells and includes passive diffusion, active transport, and carrier-mediated transport. Paracellular transport is between cell junctions. Vesicular transport involves endocytosis within cells.
3. The most common mechanism is passive diffusion, which does not require energy. Other mechanisms like active transport and carrier-mediated transport use

ONE COMPARTMENT OPEN MODEL I.V BOLUS (Contact me: dr.m.bharathkumar@gmail.com)

ONE COMPARTMENT OPEN MODEL I.V BOLUS (Contact me: dr.m.bharathkumar@gmail.com)DR. METI.BHARATH KUMAR

The document appears to be a scanned receipt from a grocery store listing various food and household items purchased totaling $123.45. It includes the store name, date, time of purchase, payment method (credit card), and signature of the cashier. The receipt provides details of the transaction including item names, quantities, and individual prices.Β

Pharmacokinetics / Biopharmaceutics - Multi compartment IV bolus

This document discusses multicompartment models used to describe drug distribution and elimination kinetics. A two-compartment model includes a central compartment representing highly perfused tissues and blood, and a peripheral tissue compartment with slower drug distribution. The plasma concentration curve following intravenous administration has an initial rapid distribution phase as the drug distributes between compartments, followed by a slower elimination phase as the drug is removed from the central compartment. Rate constants describe drug transfer between compartments, and parameters like volume of distribution and half-life can be estimated from the curve.

Non linear pharmacokinetics and different volumes of distribution

This document discusses linear and nonlinear pharmacokinetics. Linear pharmacokinetics follow first-order kinetics and nonlinear pharmacokinetics follow Michaelis-Menten kinetics. Nonlinearity can occur due to saturation of drug absorption, distribution, metabolism or excretion processes. The Michaelis-Menten equation can describe nonlinear kinetics and data plots of drug concentration versus time can indicate nonlinear behavior.

P h partition hypothesis

The document discusses the pH partition hypothesis, which states that the absorption of drugs across biomembranes is governed by the drug's dissociation constant (pKa), lipid solubility of the un-ionized form, and the pH of the absorption site. According to the hypothesis, only the un-ionized form of an acid or base drug can be absorbed if it is sufficiently lipid soluble. The fraction of a drug in its un-ionized form can be calculated using the Henderson-Hasselbach equation based on the drug's pKa and the pH. However, the pH partition theory is an oversimplification and does not always accurately predict drug absorption behavior.

Measurements of bioavailability

This document discusses measurements of bioavailability. It defines bioavailability and bioequivalence. There are two main methods to measure bioavailability - pharmacokinetic and pharmacodynamic. Pharmacokinetic methods include plasma level time studies and urinary excretion studies which measure parameters like Cmax, Tmax, and AUC from plasma data or urinary excretion rate and amount excreted from urine data. Pharmacodynamic methods include measuring acute pharmacological responses or therapeutic responses but have disadvantages like variable individual responses.

WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)

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.

METHOD OF RESIDUALS

This document presents information on estimating the absorption rate constant using the method of residuals. It discusses absorption and compartment models, outlines the steps of the method of residuals for a one compartment model, and notes considerations like lag time, flip-flop phenomena, and applications and limitations of the method. The method involves plotting drug concentrations over time, obtaining slopes for the terminal and residual lines to determine the absorption and elimination rate constants. It is best suited for rapidly absorbed drugs following one-compartment kinetics.

Bioavailability and bioequivalence

Bioavailability and bioequivalence

Β

Non linear pharmacokinetics

Non linear pharmacokinetics

Β

Introduction to biopharmaceutics

Introduction to biopharmaceutics

Β

Bioavailability and bioequivalence

Bioavailability and bioequivalence

Β

PHARMACOKINETIC MODELS

PHARMACOKINETIC MODELS

Β

Techniques for enhancement of dissolution rate

Techniques for enhancement of dissolution rate

Β

In vitro Dissolution Testing Models

In vitro Dissolution Testing Models

Β

Non linear biopharmaceutics

Non linear biopharmaceutics

Β

Absorption of drugs from non per os extravascular administration

Absorption of drugs from non per os extravascular administration

Β

Compartment modeling

Compartment modeling

Β

In-Vivo In-Vitro Correlation

In-Vivo In-Vitro Correlation

Β

Two compartment open model sulekhappt.x.1

Two compartment open model sulekhappt.x.1

Β

Mechanism of drug absorption in git

Mechanism of drug absorption in git

Β

ONE COMPARTMENT OPEN MODEL I.V BOLUS (Contact me: dr.m.bharathkumar@gmail.com)

ONE COMPARTMENT OPEN MODEL I.V BOLUS (Contact me: dr.m.bharathkumar@gmail.com)

Β

Pharmacokinetics / Biopharmaceutics - Multi compartment IV bolus

Pharmacokinetics / Biopharmaceutics - Multi compartment IV bolus

Β

Non linear pharmacokinetics and different volumes of distribution

Non linear pharmacokinetics and different volumes of distribution

Β

P h partition hypothesis

P h partition hypothesis

Β

Measurements of bioavailability

Measurements of bioavailability

Β

WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)

WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)

Β

METHOD OF RESIDUALS

METHOD OF RESIDUALS

Β

Concept of nonlinear pharmacokinetic

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

NONLINEAR PHARMACOKINETICS_ppt.pdf

The document discusses linear and nonlinear pharmacokinetics. It defines linear pharmacokinetics as processes where the rate is proportional to dose and pharmacokinetic parameters are unaffected by dose. Nonlinear pharmacokinetics occurs when rates become dose-dependent due to saturation of carriers, enzymes or receptors. It describes methods to detect nonlinearity including determining parameters at different doses. Causes include saturation of absorption, distribution, metabolism and excretion processes. The Michaelis-Menten equation is presented as a way to model saturable processes and methods to estimate Km and Vmax values are outlined, including at steady state concentrations.

Non linear kinetics

Non-linear pharmacokinetics can occur when drug absorption, distribution, or elimination processes become saturated at high drug concentrations. This can cause the rate of drug clearance to change from first-order to zero-order kinetics with increasing doses. Non-linear kinetics results in plasma concentrations and pharmacokinetic parameters that are not proportional to the administered dose. Specific causes include saturation of drug metabolizing enzymes, plasma protein binding sites, or renal reabsorption/secretion mechanisms. Non-linear drugs have less predictable responses and greater potential for toxicity compared to linearly eliminated drugs.

Non linear pharmacokinetics

Detection of non-linearity in pharmacokinetics
Causes of nonlinearity
Michaelis β Menten equation
Estimation of Km and Vmax

Nonlinear pharmacokinetic

- The document discusses nonlinear pharmacokinetics where parameters like clearance and volume of distribution change with dose. This occurs when transporters or enzymes involved in absorption, distribution, metabolism and excretion get saturated at high drug concentrations.
- The Michaelis-Menten equation is used to describe saturation kinetics and estimate parameters Km and Vmax. Various methods like Lineweaver-Burk, direct linear and graphical plots are presented to determine these values using in vivo or in vitro concentration and rate data.
- Estimation of Km and Vmax is also described at steady-state concentrations achieved after constant rate infusion or multiple dosing, through plots of steady-state concentration versus dosing rate.

A seminar on one & two compartment open model extra vascular administration

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This document summarizes one and two compartment open models for extravascular drug administration. It describes how compartment models are used to simplify drug distribution and elimination processes in the body. A one compartment open model is presented, showing drug absorption from extravascular administration followed by distribution and elimination from the body compartment. Equations are provided to describe drug behavior under zero-order and first-order absorption. Methods for estimating the absorption rate constant like residuals and Wagner-Nelson are also summarized. Finally, a two compartment open model is briefly introduced.Β

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This document discusses pharmacokinetics and provides information about key concepts used in pharmacokinetics including:
- Logarithms and how they relate to calculating drug concentrations over time
- Differential and integral calculus which are used to develop equations to model rates of change in drug absorption and elimination over small time intervals
- How to write differential equations to model different rate processes like zero-order, first-order, and Michaelis-Menten kinetics
- The use of graphs including Cartesian and semi-log scales to plot drug concentration vs. time profiles
- Examples of using these concepts to solve pharmacokinetic problems

Nonlinear Pharmacokinetics

Nonlinear pharmacokinetics occurs when the body's processing of a drug is saturated at higher doses, causing kinetics parameters like clearance and half-life to change with dose. Michaelis-Menten kinetics are commonly used to model nonlinear metabolism, where the metabolic rate approaches a maximum (Vmax) at high concentrations. Parameters like Vmax and KM can be estimated from steady-state dosing and concentration data by linearizing the Michaelis-Menten equation. Drugs like phenytoin exhibit nonlinear kinetics due to capacity-limited hepatic metabolism.

kinetics (Lec 2).pptx

This document discusses pharmacokinetics and pharmacokinetic modeling. It begins with an introduction to first order kinetics and the equations used to describe first order reactions. It then discusses compartment modeling, describing one, two, and multi-compartment models. The document provides examples of pharmacokinetic parameters including elimination rate constant, volume of distribution, and fraction unbound. It concludes with an overview of linear vs non-linear pharmacokinetics and steady state concentrations.

PHARMACOKINETICS: BASIC CONSIDERATION & PHARMACOKINETIC MODELS

Plasma Drug Concentration Time Profile
Pharmacokinetic Parameter
Pharmacodynamic Parameter
Zero, First Order & Mixed Order Kinetic
Rates & Order Of Kinetics
Pharmacokinetic Models
Application Of Pharmacokinetic

Pharacokinetics power point for pharmacy

The document discusses various pharmacokinetic models used to describe drug movement in the body. It begins by defining pharmacokinetics and some key parameters. It then describes compartment models, including mammillary and caternary models, and provides an example of a one-compartment open model for intravenous bolus administration. This model assumes rapid distribution and first-order elimination. The document also discusses zero-order and first-order reaction kinetics and how they relate to pharmacokinetic processes. It provides examples of using compartment model equations to calculate drug concentrations over time and dosing requirements.

Michaelis menten kinetics Nonlinear Pharmacokinetics

The saturable concentration when the velocity of the reaction is equal to half of the maximum velocity or 0.5 V max

Pharmacokinetic models

PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).

Pharmacokinetic Models

1. The document outlines a lecture on pharmacokinetic models, which provide mathematical descriptions of how drugs move through the body over time.
2. Pharmacokinetic models are classified as compartmental models, non-compartment models, or physiological models. Compartmental models divide the body into compartments and use rate constants to describe drug movement between compartments.
3. Key pharmacokinetic parameters like volume of distribution, elimination rate constant, half-life, and clearance can be calculated from compartmental model equations to quantify a drug's absorption, distribution, metabolism, and excretion.

Non linear Pharmacokinetics 2

Here are the steps to solve this problem:
a. At a dose of 10 mg/kg, the plasma concentration would be 10 mg/kg / 20 L/kg = 0.5 mg/L = 500 ΞΌg/mL. Since this concentration is greater than the KM value of 50 ΞΌg/mL, the reaction order for metabolism would be zero order.
b. For zero order kinetics, the rate of elimination is equal to Vmax. So the time for 50% elimination is the dose (10 mg/kg) x 0.5 / Vmax. Vmax is given as 20 ΞΌg/mL/hr = 20 mg/kg/hr. Therefore, the time is 10 mg/kg x 0.5 / 20

Compartment Modelling

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.

Determination of absorption and elimination rates on base of compartment model

This document provides information about determining absorption and elimination rates using compartment models. It discusses what compartment models are and describes one-compartment open models. It explains zero-order and first-order absorption models and how to calculate elimination rate constants. The document also discusses using urinary excretion data to estimate pharmacokinetic parameters when plasma concentration data is unavailable. Parameters like volume of distribution, clearance, excretion and elimination rate constants can be estimated from urinary excretion data using methods like the rate of excretion method.

Determination of absorption and elimination rates on base of compartment model

This document provides information about determining absorption and elimination rates using compartment models. It discusses the concepts of absorption, elimination, and compartment models. It then describes the one-compartment open model and differences between zero-order and first-order absorption kinetics. The document outlines the absorption and elimination phases when following one-compartment kinetics. It also discusses using urinary excretion data to determine pharmacokinetic parameters when plasma level data is unavailable. The document was prepared by Abhinay Ashok Jha for his final year assessment on this topic.

01_AJMS_331_21.pdf

This document reviews open two compartment pharmacokinetic models. It discusses how a drug administered intravenously distributes between a central (plasma) compartment and peripheral (tissue) compartment. The fate of the drug in the compartments is estimated using Laplace transforms to derive mathematical formulas relating the drug concentrations over time. These formulas contain hybrid constants that can be used to calculate the pharmacokinetic parameters k, k12, and k21, which describe the drug distribution and elimination rates between compartments. The tissue concentration and biological half-life of the drug can then be predicted from these parameter values.

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- 1. PRESENTED BY: Deepak A. Thakre M.Pharm I Year Industrial Pharmacy Department Shri Sadashivrao Patil Shikshan Sanstha's SMT. KISHORITAI BHOYAR COLLEGE OF PHARMACY, KAMPTEE GUIDED BY : Dr. Jayshree B. Taksande HOD Pharmaceutics Department TOPIC : 1. The Michaelis-Menten equation & 2. Estimating Km and Vmax 1
- 2. ο If metabolism is the only pathway of elimination, the rate of metabolism or elimination is defined by the Michaelis-Menten equation. ο The (Non- linear) kinetics of capacity-limited or saturable processes is best described by Michaelis-Menten equation: β π π π π = π½ππππͺ ππ¦+π ------- (1) Where, βdc/dt = rate of decline of drug concentration with time, Vmax = theoretical maximum rate of the process, Km = Michaelis constant, C= drug Concentration . ο Three situations can now be considered depending upon the values of Km and C: A] When Km = C ο Under this situation, the equation (1) reduces to i.e. β ππ ππ‘ = ππππ₯ 2 -------(2) i.e. the rate of process is equal to one-half its maximum rate. 2
- 3. 3 A plot of Michaelis-Menten equation (elimination rate dC/dt versus concentration C). Initially, the rate increases linearly (first-order) with concentration, becomes mixed-order at higher concentration and then reaches maximum (Vmax) beyond which it proceeds at a constant rate (zero-order).
- 4. Michaelis-Menten equation is generally used to explain the kinetics of in-vitro, few enzyme catalyzed in-vivo and in-situ processes. 4
- 5. 5 B] Km>> C When the concentrations are low, i.e. Km> C, then Km +C is approximately equal to Km, β π π π π = ππ¦ππ±π ππ¦ ------------ equation .(3) The above equation is identical to the one that describes first-order elimination of a drug where Vmax/Km = KE. This 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. Because both Vmax and Km are constants, the metabolism rate is proportional to the drug concentration and is constant (i.e., first-order process).
- 6. C] C>> Km When the concentrations are high, i.e. C > Km, then π π π π = π½ππππͺ πͺ = π½πππ ------- equation (4) Equation 4 gives the zero order kinetics. Therefore, it was concluded that at high plasma concentrations, first order kinetics were not seen. The above equation is identical to the one that describes a zero-order process i.e. the rate process occurs at a constant rate Vmax and is independent of drug concentration. ο When given in therapeutic doses, most drugs produce plasma drug concentrations well below the Km for all carrier mediated enzyme systems affecting the pharmacokinetics of the drug. ο Hence most of the drugs at normal therapeutic concentrations follow 1st order rate processes. Some of the drugs like phenytoin and salicylate saturate the hepatic mixed function oxidases at higher therapeutic doses. ο With these drugs, elimination kinetics is 1st order at low doses and mixed at high doses and shows zero-order at very high therapeutic doses. 6
- 7. If a single IV bolus injection of drug D0 is given at t=0, the drug concentration, Ct in the plasma at any time may be calculated by integrated form of Eq 1 is given by πͺπβπͺπ π = π½πππ β π²ππͺ π π°π πͺπ π ----equation (5) Where C0 is the concentration at time t=0. Alternatively the amount of the drug in the body after an IV bolus injection may be calculated by the following relationship. π«πβπ«π π = π½πππ β π²ππͺ π π°π π«π π ------equation (6) Where Do is the amount of the drug in the body at t=0. β¦Equation (5) β¦Equation (6) Equation 6 can be used to study the decline of the drug in the body after the administration of different therapeutic doses. Here, the Km and Vmax of the drug are unknown. 7
- 8. By rearranging the above Equation 6, time to decline a certain amount of the dose of a drug can be calculated by the following equation π‘ = 1 ππππ₯ π·π β π·π‘ + πΎπ πΌπ π·π π·π‘ -----equation (7) Equation 7 explains an inverse relationship between the time for the dose to decline to a certain amount of the drug in the body and Vmax. οActually, Km can be said as the hybrid constant in enzyme kinetics that may represents both forward as well as backward reaction. οIt is equivalent to the concentration of the drug in the body at Β½ Vmax. οThe one compartment open model having capacity limited elimination pharmacokinetics effectively explains the plasma drug concentration time profiles for a number of drugs. 8
- 9. 9 The parameters of capacity-limited processes like metabolism, renal tubular secretion and biliary excretion can be easily defined by assuming one-compartment kinetics for the drug and that elimination involves only a single capacity-limited process. The parameters Km and Vmax can be assessed from the plasma concentration-time data collected after i.v. bolus administration of a drug with nonlinear elimination characteristics. Rewriting equation β π π π π = π½ππππͺ ππ¦+π ---------equation (1) Integration of above equation followed by conversion to log base 10 yields: ππππͺ = πππ ππ¨ + ππ¨βπ π.πππππ¦ β ππ¦ππ± π.πππππ¦ -------(2) Estimating Km and Vmax
- 10. 10 A semilog plot of C versus t yields a curve with a terminal linear portion having slope βVmax/2.303Km and when back extrapolated to time zero gives Y- intercept log Co .The equation that describes this line is: Fig: Semi-log plot of a drug given as i.v. bolus with nonlinear elimination and that fits one-compartment kinetics. ----equation (3)
- 11. 11 From equation 2 and 3 ( at low Plasma Concentration) πΏπππΆπ = ππππΆπ + πΆπβπΆ 2.303πΎπ ππππΆπ β ππππΆπ = πΆπβπΆ 2.203πΎπ OR πππ πΆπ πΆπ = πΆπβπΆ 2.303πΎπ For this equation Km can be obtained. Vmax can be Computed by Substituting the value of Km in the Slope value.
- 12. Estimating Km and Vmax Method : Equation 1 gives the relationship of the drug biotransformation to the concentration of the drug in the body. When an experiment is performed by using different concentrations of the drug C, a series of reaction rates (V) may be calculated for each concentration. Km and Vmax can then be determined by using the special plots. Hence, V= π½ππππͺ ππ¦+π ------ equation (8) Rearranging the above equation 8, [As Per Equation of Slope- π = ππ + π] 1 π = πΎπ ππππ₯ 1 πΆ + 1 ππππ₯ -----equation (9) Above Equation 9 gives the linear equation, when 1/V is plotted against 1/C, the resultant intercept for the line is 1/Vmax and the slope is Km/Vmax Fig: Plot of 1/V against 1/C for the determination of Km and Vmax 12
- 13. 13