ADME And PHARMACOKINETICS.

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Presentation transcript:

ADME And PHARMACOKINETICS

ADME lecture 1 Contents ... What are ADME and Pharmacokinetics? Absorption Distribution

What are ADME and pharmacokinetics? Part 1 What are ADME and pharmacokinetics?

PHARMACOKINETICS “Drug movement” (Greek) Mathematical description of the various processes that constitute ADME.

ADME Absorption Distribution Metabolism Excretion Elimination

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.

Distribution The 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 …

Elimination The 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.

Part 2 Absorption

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.

Passive diffusion Lipid Water DRUG

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

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.

Part 3 Distribution

Distribution Kidneys Fat Blood etc Liver

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 Lipid Total drug concentration in blood greater than in cell.

Intra-cellular binding BLOOD CELL Drug Drug Drug.Protein Lipid Nucleic acid Lipid Total drug concentration in blood lower than in cell.

Overall binding BLOOD CELL Drug Drug Drug.Protein Drug.Protein Lipid Nucleic acid Lipid Balance depends upon relative binding affinity in blood and tissues.

Terms with which you should be familiar ... ADME Pharmacokinetics Absorption Passive diffusion Distribution Faciliated diffusion Metabolism Active transport Excretion Elimination

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