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PHARMACOKINETIC MODELS
OUTLINE
At the end of this lecture, student will learn
about:
• What is a model?
• Types of Pharmacokinetic models
INTRODUCTION
• Drugs are in a dynamic state within the body as
they move between tissues and fluids, bind with
plasma or cellular components, or are metabolized.
• The inherent and infinite complexity of these events
require the use of mathematical models and
statistics to estimate drug dosing and to predict the
time course of drug efficacy for a given dose .
• A model is a hypothesis using mathematical terms to
describe quantitative relationships concisely.
• The predictive capability of a model lies in the proper
selection and development of mathematical function
INTRODUCTION
• A pharmacokinetic parameter is a constant for the
drug that is estimated from the experimental data
• The key parameters in a process are commonly
estimated by fitting the model to the experimental
data, known as variables.
INTRODUCTION
• Such mathematical models can be devised to simulate
the rate processes of drug absorption, distribution,
and elimination to describe and predict drug
concentrations in the body as a function of time .
• Pharmacokinetic models are used to:
1. Predict plasma, tissue, and urine drug levels with any
dosage regimen
2. Calculate the optimum dosage regimen for each
patient individually
INTRODUCTION
3. Estimate possible accumulation of drugs and metabolites
4. Correlate drug concentrations with pharmacologic or
toxicologic activity
5. Evaluate differences in the rate or extent of
availability between formulations (bioequivalence)
6. Describe how changes in physiology or disease affect
the absorption, distribution, or elimination of the drug
7. Explain drug interactions
INTRODUCTION
• A model may be empirically, physiologically, or
compartmentally based.
• Empirical model - simply interpolates the data and
allows an empirical formula to estimate drug level
over time
ojustified when limited information is available
oPractical but not very useful in explaining the
mechanism of the actual process
PHARMACOKINETIC MODELS
PHARMACOKINETIC MODELS
• The models describe the data kinetically, with the
consideration that blood flow is responsible for
distributing drug to various parts of the body.
• Uptake of drug into organs is determined by the
binding of drug in these tissues.
Drawbacks with this model are:
• What is the meaning of concentration in the tissue?
• Concentration in tissue and blood in the organ
• Specimen collection is difficult
Lecture 8.pdf
PHARMACOKINETIC MODELS
• Physiological based pharmacokinetic models can
be applied to several species and human data may be
extrpolated.
• On the basis of blood flow, tissues are divided into:
• Rapidly equilibrating tissue (RET)
• Slowly equilibrating tissue (SET)
• Examples of drugs are digoxin, lidocaine and methotrexate
PHARMACOKINETIC MODELS
• A very simple and useful tool in pharmacokinetics is
compartmentally based models
• Assume a drug is given by intravenous injection
• Exemplified as a tank containing a volume of fluid
that is rapidly equilibrated with the drug.
• Concentration of the drug in the tank is governed by:
(1) the fluid volume of the tank
(2) elimination rate of drug
• Fluid-filled tank model id called the one
compartment open model
PHARMACOKINETIC MODELS
• Compartment models are based on linear
assumptions using linear differential equations .
• As the number of parameters required to model data
increases, accurate estimation becomes more difficult.
• Because a model is based on a hypothesis and
simplifying assumptions, a certain degree of caution is
necessary when relying totally on the pharmacokinetic
model to predict drug action.
PHARMACOKINETIC MODELS
• Drug kinetics in the body are frequently represented
by one or more tanks, or compartments, that
communicate with each other.
• A compartment is not a real physiologic or anatomic
region but is considered as a tissue or group of
tissues that have similar blood flow and drug affinity.
• Within each compartment, mixing of the drug rapid
and homogeneous and is "well stirred"
Lecture 8.pdf
Lecture 8.pdf
PHARMACOKINETIC MODELS
Types of compartment models
• Mammillary model -
compartments around a central
compartment like satellites.
• Catenary model - compartments joined to one another
like the compartments of a train.
SUMMARY
• What is a model?
• Types of Pharmacokinetic models:
• Empirical model
• Physiological model
• Compartment based model

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Lecture 8.pdf

  • 2. OUTLINE At the end of this lecture, student will learn about: • What is a model? • Types of Pharmacokinetic models
  • 3. INTRODUCTION • Drugs are in a dynamic state within the body as they move between tissues and fluids, bind with plasma or cellular components, or are metabolized. • The inherent and infinite complexity of these events require the use of mathematical models and statistics to estimate drug dosing and to predict the time course of drug efficacy for a given dose .
  • 4. • A model is a hypothesis using mathematical terms to describe quantitative relationships concisely. • The predictive capability of a model lies in the proper selection and development of mathematical function INTRODUCTION
  • 5. • A pharmacokinetic parameter is a constant for the drug that is estimated from the experimental data • The key parameters in a process are commonly estimated by fitting the model to the experimental data, known as variables. INTRODUCTION
  • 6. • Such mathematical models can be devised to simulate the rate processes of drug absorption, distribution, and elimination to describe and predict drug concentrations in the body as a function of time . • Pharmacokinetic models are used to: 1. Predict plasma, tissue, and urine drug levels with any dosage regimen 2. Calculate the optimum dosage regimen for each patient individually INTRODUCTION
  • 7. 3. Estimate possible accumulation of drugs and metabolites 4. Correlate drug concentrations with pharmacologic or toxicologic activity 5. Evaluate differences in the rate or extent of availability between formulations (bioequivalence) 6. Describe how changes in physiology or disease affect the absorption, distribution, or elimination of the drug 7. Explain drug interactions INTRODUCTION
  • 8. • A model may be empirically, physiologically, or compartmentally based. • Empirical model - simply interpolates the data and allows an empirical formula to estimate drug level over time ojustified when limited information is available oPractical but not very useful in explaining the mechanism of the actual process PHARMACOKINETIC MODELS
  • 9. PHARMACOKINETIC MODELS • The models describe the data kinetically, with the consideration that blood flow is responsible for distributing drug to various parts of the body. • Uptake of drug into organs is determined by the binding of drug in these tissues. Drawbacks with this model are: • What is the meaning of concentration in the tissue? • Concentration in tissue and blood in the organ • Specimen collection is difficult
  • 11. PHARMACOKINETIC MODELS • Physiological based pharmacokinetic models can be applied to several species and human data may be extrpolated. • On the basis of blood flow, tissues are divided into: • Rapidly equilibrating tissue (RET) • Slowly equilibrating tissue (SET) • Examples of drugs are digoxin, lidocaine and methotrexate
  • 12. PHARMACOKINETIC MODELS • A very simple and useful tool in pharmacokinetics is compartmentally based models • Assume a drug is given by intravenous injection • Exemplified as a tank containing a volume of fluid that is rapidly equilibrated with the drug. • Concentration of the drug in the tank is governed by: (1) the fluid volume of the tank (2) elimination rate of drug
  • 13. • Fluid-filled tank model id called the one compartment open model
  • 14. PHARMACOKINETIC MODELS • Compartment models are based on linear assumptions using linear differential equations . • As the number of parameters required to model data increases, accurate estimation becomes more difficult. • Because a model is based on a hypothesis and simplifying assumptions, a certain degree of caution is necessary when relying totally on the pharmacokinetic model to predict drug action.
  • 15. PHARMACOKINETIC MODELS • Drug kinetics in the body are frequently represented by one or more tanks, or compartments, that communicate with each other. • A compartment is not a real physiologic or anatomic region but is considered as a tissue or group of tissues that have similar blood flow and drug affinity. • Within each compartment, mixing of the drug rapid and homogeneous and is "well stirred"
  • 18. PHARMACOKINETIC MODELS Types of compartment models • Mammillary model - compartments around a central compartment like satellites. • Catenary model - compartments joined to one another like the compartments of a train.
  • 19. SUMMARY • What is a model? • Types of Pharmacokinetic models: • Empirical model • Physiological model • Compartment based model