Pharmacokinetics – Absorption & Distribution

Pharmacokinetics Overview

  • Pharmacokinetics (ADME): Absorption→Distribution→Metabolism→Excretion\text{Absorption} \rightarrow \text{Distribution} \rightarrow \text{Metabolism} \rightarrow \text{Excretion}
  • Lecture focus: Absorption + Distribution ("AD" of ADME)

Absorption

  • Definition: Movement of drug from site of administration to bloodstream.
  • Oral route: majority absorbed in small intestine (large surface area, longer transit time).
  • Non-GI routes (IV, buccal/sublingual, parenteral, transdermal) bypass GI tract ➔ faster systemic entry.
Key Determinants of Absorption
  1. Dosage form: liquids > tablets/capsules (no dissolution step).
  2. Route of administration: \text{IV} > \text{IM} > \text{SC} > \text{oral} (speed).
  3. Drug chemistry:
    • Size: smaller molecules diffuse more readily.
    • Lipid solubility: lipophilic drugs cross membranes easily.
    • Enteric coating delays gastric dissolution ➔ intestinal absorption.
  4. pH & ionisation:
    • Acidic stomach vs. alkaline intestine influences ionisation state.
    • Non-ionised forms cross membranes; ionised forms remain in lumen.
  5. Gastric factors: acidity fluctuations (food, age), gastric emptying, presence of food/drugs.
  6. Surface area: larger area ➔ higher absorption (small intestine).
  7. Blood flow at site: ↑ flow (heat) speeds uptake; ↓ flow (cold) slows.

Distribution

  • Definition: Movement of drug from bloodstream to target tissues.
Key Determinants of Distribution
  1. Tissue perfusion: high in brain/heart ➔ rapid; low in bone/adipose ➔ slow.
  2. Physical properties:
    • Lipid-soluble (lipophilic) cross membranes easily.
    • Water-soluble (hydrophilic) remain in plasma/interstitial fluid and need transporters.
  3. Biological barriers:
    • Blood–brain barrier: tight, restricts many drugs.
    • Placental barrier: less restrictive; fetal exposure possible.
  4. Plasma protein binding:
    • Main carriers: albumin (acidic drugs), globulin (basic drugs).
    • Bound fraction = inactive reservoir; free fraction = pharmacologically active.

Drug Reservoirs & Volume of Distribution (Vd)

  • Adipose tissue: stores lipophilic drugs ➔ prolonged presence (e.g., THC).
  • Plasma proteins: temporary storage; regulate free drug concentration.
  • Hydrophilic drugs stay in extracellular fluid, need carriers to enter cells.
  • Volume of distribution: extent drug leaves plasma for tissues; higher tissue uptake = higher VdV_d.