Drug Absorption and Distribution

Question 1

Define:

• Drug deposition
• Absorption
• Distribution
• Metabolism
• Excretion

Answer 1

• Drug deposition: the fate of drugs in the body
• Absorption: the process by which a drug enters the body from its site of administeration and enters the general circulation
• Distribution: the transport of drug by general circulation. Drugs most often leave the blood and enter perfused tissues
• Metabolism: the process by which tissue enzymes i the liver catalyse the chemical conversion of a frequently lipid soluble drug to an often less active and more polar form that is more readily excreted from the body
• Excretion: the processes that remove the drug, or its metabolites from the body (principally the kidneys)

Question 2

Name some factors controlling drug absorption from the GI Tract:

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What is the partition coefficient?

Answer 2

• solubility: the drug must dissolve in an aqueous environment in order to be absorbed
• chemical stability: some drugs are destroyed by acid in the stomach or enzymes in the GIT, sometimes a compound is modified within the gut to release the active drug
• lipid to water partition coefficient: absorption of a drug occurs by simple diffucion across membranes. For a given drug concentration gradient across a membrane, the rate of diffusion increases with the lipid solubility of the drug

The partition coefficient is the ratio of the drug concentration in the membrane and concentration in water at equilibrium.

Question 3

Do acidic drugs become more or less ionised in an acid environment?

Do basic drugs become more or less ionised in a basic environment?

Where does the majority of absorption occur?

What are absorbed well and which are poorly absorbed?

Answer 3

Acidic drugs become less ionised in an acid environment and basic drugs become less ionised in a basic environment.

The majority of absorption occurs in the small intestine as it has a large surface area.

Weak acids and weak bases are well absorbed, strong acids and strong bases are poorly absorbed.

Question 4

Factors affecting gastrointestinal absorption:

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Answer 4

• gastrointestinal motility
• pH
• blood flow
• the way in which the tablet is manufactured
• physicochemical interactions

presence of transporters in the membranes of epithelial cells of the GIT

Question 5

Define oral availability:

Define systemic availability:

Answer 5

Oral availability is the fraction of drug that reaches the systemic circulation after oral ingestion (amount in systemic circulation/amount administered)

Systemic availability is the fraction that reaches the systemic circulation after absorption (amount in systemic circulation/amount absorbed)

Drugs administered intravenously have 100% systemic availability