Pharmacokinetics: Absorption and Distribution

Pharmacokinetics Overview

• Pharmacokinetics encompasses the processes of drug movement into, through, and out of the body.
• The acronym ADMI stands for:
  • Absorption: Movement of the drug into the bloodstream from the site of administration.
  • Distribution: Movement of the drug to its site of action via the bloodstream.
  • Metabolism: Breakdown of the drug to prevent accumulation in the body.
  • Excretion: Removal of the drug from the body.

Absorption

• Definition: The process by which a drug moves from the site of administration into the bloodstream.
• Key Points:
  • Drugs must be dissolved for absorption, particularly when administered orally through the gastrointestinal (GI) tract, with maximum absorption occurring in the small intestine due to its large surface area.
  • Intravenous (IV) administration bypasses the GI tract, delivering drugs directly into systemic circulation.
• Factors Affecting Absorption:
  • Physical Form of Drug:
  • Liquids are absorbed faster than tablets or capsules because they do not require breakdown.
  • Route of Administration:
  • IV: Direct entry into systemic circulation; fastest absorption.
  • Buccal and sublingual routes provide rapid access to the bloodstream through the mucous membranes.
  • Parenteral injections (subcutaneous and intramuscular):
    • Subcutaneous injection has slower absorption due to less blood flow than intramuscular injections.
  • Chemical Nature of Drug:
  • Smaller drugs diffuse faster across membranes.
  • Enteric Coating: Designed to withstand gastric acidity, releasing the drug in the alkaline environment of the small intestine.
  • Acidity and pH: Influences absorption, with different acidity levels throughout the day affecting drug breakdown and absorption rates.
  • Surface Area of Absorption:
  • Small intestine: The primary site for the majority of drug absorption due to extensive surface area and prolonged transit time.
  • Blood Flow: Higher blood flow increases absorption rates; hot packs increase local blood flow, aiding drug absorption; cold packs decrease regional blood flow, impeding absorption.
  • Lipid Solubility: Lipid-soluble substances pass easily through cell membranes, leading to enhanced absorption; hydrophilic substances often remain in water-based environments.
  • Degree of Ionization: Influenced by pH; non-ionized drugs are more likely to be absorbed, while ionized drugs tend to remain in local compartments.

Distribution

• Definition: The process of drug movement from the site of absorption to the site of action.
• Key Factors Influencing Distribution:
  • Blood Supply to Tissues:
  • Organs like the brain and heart receive rich blood supply, allowing quick drug distribution; bones have lower blood supply, leading to slower distribution.
  • Physical Properties of Drug:
  • Lipophilic drugs easily cross membranes, while hydrophilic drugs require transporters to facilitate movement across membranes.
  • Barriers:
  • Blood-Brain Barrier: Highly selective barrier that restricts certain drugs from crossing; important for protecting neural tissue.
  • Placental Barrier: Less selective than the blood-brain barrier, allowing some drugs to cross and potentially affect the fetus.
• Drug Binding and Storage:
  • Plasma Proteins:
  • Two primary carriers are Albumin (binds acidic drugs) and Globulin (binds basic drugs).
  • Drugs can be found in two forms:
  • Free Form: Active and can exert effects at the site of action.
  • Protein-Bound: Inactive as they are attached to plasma proteins, requiring release to become active.
  • Adipose Tissue: Acts as a storage site for lipophilic drugs, possibly delaying their effects and elimination.
  • Hydrophilic Drugs: Tend to remain in interstitial spaces and may require transport mechanisms to cross membranes.
• Volume of Distribution (Vd):
  • Indicates the extent of drug distribution throughout the body's tissues; higher Vd means more extensive distribution.