Dr Phil Rowe School of Pharmacy

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Dr Phil RoweSchool of Pharmacy ChemistryJohn
Moores UniversityLiverpool
ADME
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ADME lecture 1Contents ...

• What are ADME and Pharmacokinetics?
• Absorption
• Distribution

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Part 1
What are ADME and pharmacokinetics?
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ADME

• Absorption
• Distribution
• Metabolism
• Excretion

Elimination
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Absorption The movement of drugs into the body
Do not consider a drug to be fully absorbed until
it reaches the blood stream. Drugs administered
orally, intramuscularly, subcutaneously etc need
to undergo absorption (unless effect is to be
topical). Only i.v. route does not require
absorption.
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DistributionThe movement of drugs around the body
Once absorbed, drugs will generally move around
the body. A drug molecule may spend some time in
one organ, then be carried by the blood to
another organ and so on
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EliminationThe removal of drugs from the body

• Elimination is the final removal of the drug from
  the body. This is subdivided into
• Metabolism Destruction of the drug by chemical
  alteration.
• Excretion Removal of the drug from the body
  (Generally in the urine). Note that the term
  Excretion is only used if the drug is removed
  chemically unaltered.

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PHARMACOKINETICS

• Drug movement (Greek)
• Mathematical description of the
• various processes that constitute
• ADME.

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Part 2
Absorption
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Absorption

• Three mechanisms by which drugs may cross
  membranes
• Passive diffusion
• Facilitated diffusion
• Active transport
• Passive diffusion MUCH more common than any of
  the others.

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Passive diffusion
DRUG
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Requirements for passive diffusion

• Water solubility
• Lipid solubility

• Almost all drugs are sufficiently water soluble
  to undergo passive diffusion, but some do lack
  the necessary lipid solubility.
• In practice, passive diffusion depends mainly on
  lipid solubility.

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Specificity of passive diffusion

• Non-specific. No requirements as to the
• size or shape of the molecule, just so long
• as it is lipid soluble.

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Efficiency of passive diffusion
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Facilitated diffusion and active transport

• Both operate via a transport protein that
  carries a molecule across a membrane.
• Active transport is energy requiring, but
  facilitated diffusion is not.
• The transport proteins will only carry
  structurally specific groups of molecules e.g.
  amino acids
• Very few drugs have structures sufficiently
  similar to any naturally occurring group of
  molecules that have a carrier protein. Therefore
  rarely arises.

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Part 3
Distribution
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Distribution
Kidneys
Fat
Blood
etc
Liver
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Factors influencing distribution of a drug

• Ability to undergo passive diffusion (Already
  described)
• Binding to macromolecules

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Plasma protein binding
BLOOD
CELL
Drug
Drug
Drug.Protein
Lipid
Total drug concentration in blood greater than in
cell.
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Intra-cellular binding
BLOOD
CELL
Drug
Drug
Drug.Protein Lipid Nucleic
acid
Lipid
Total drug concentration in blood lower than in
cell.
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Overall binding
BLOOD
CELL
Drug
Drug
Drug.Protein
Drug.Protein Lipid Nucleic
acid
Lipid
Balance depends upon relative binding affinity in
blood and tissues.
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Terms with which you should be familiar ...
ADME Pharmacokinetics Absorption
Passive diffusion Distribution
Faciliated diffusion Metabolism Active
transport Excretion Elimination
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What you should be able to do

• Distinguish between metabolism and excretion
• Describe the mechanism of passive diffusion
• Predict whether a given molecule will easily
  undergo passive diffusion
• Identify the factors that may influence the
  distribution of a given drug