ADME And PHARMACOKINETICS. ADME lecture 1 Contents... What are ADME and Pharmacokinetics? Absorption...
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Transcript of ADME And PHARMACOKINETICS. ADME lecture 1 Contents... What are ADME and Pharmacokinetics? Absorption...
PHARMACOKINETICS
“Drug movement” (Greek)
Mathematical description of the
various processes that constitute
ADME.
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.
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 …
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.
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.
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.
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.
Efficiency of passive diffusion
Efficient Inefficient Hydrocarbons Anaesthetics Alcohols Lipids Most drugs
Carbohydrates Proteins Ionised molecules
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.
Factors influencing distribution of a drug:
Ability to undergo passive diffusion (Already described)
Binding to macromolecules
Plasma protein binding
BLOOD CELL
Drug Drug
Drug.Protein
Total drug concentration in blood greater than in cell.
Lipid
Intra-cellular bindingBLOOD CELL
Drug Drug
Drug.Protein Lipid Nucleic acid
Total drug concentration in blood lower than in cell.
Lipid
Overall binding
Balance depends upon relative binding affinity in blood and tissues.
Drug.Protein Lipid Nucleic acid
BLOOD CELL
Drug Drug
Drug.ProteinLipid
Terms with which you should be familiar ...
ADME PharmacokineticsAbsorption Passive diffusionDistribution Faciliated diffusionMetabolism Active transportExcretionElimination