Pharmacokinetics: Absorption and Distribution covers pharmacokinetics — absorption and distribution for INI CET (AIIMS PG).
Pharmacokinetics (PK): What the body does to a drug — ADME: Absorption, Distribution, Metabolism, Excretion.
Absorption: Transfer of drug from site of administration into systemic circulation.
Routes of Administration:
| Route | Bioavailability | Onset | Notes |
|---|---|---|---|
| IV | 100% (bypasses absorption) | Immediate | No absorption phase; direct vascular access |
| IM | Variable (depends on drug) | Rapid | Aqueous vs oily depot formulations |
| SC | Slightly slower than IM | Rapid | Small volumes; irritant drugs avoid SC |
| Oral | Highly variable | Slower | First-pass effect reduces bioavailability |
| Sublingual | Bypasses first-pass | Rapid | Nitroglycerin, nifedipine |
| Rectal | Variable | Moderate | Partial first-pass avoidance |
| Inhalation | Rapid | Very rapid | Gases, volatile agents, bronchodilators |
| Topical | Low systemic | Local effect | Skin, eye, lung (inhaled) |
First-Pass Effect (First-Pass Metabolism):
- Drug absorbed from GI tract → portal circulation → liver before reaching systemic circulation
- Significant for drugs like propranolol, lidocaine, morphine — extensive hepatic extraction
- Consequence: Lower oral bioavailability compared to other routes
- Pro-drugs: Inactive until first-pass metabolism activates them (e.g., codeine → morphine, enalapril → enalaprilat)
Factors Affecting Absorption:
- Physicochemical: Ionization (pKa), lipid solubility, molecular size, stability
- pH partition theory: Non-ionized (lipid-soluble) form crosses cell membranes; ionized form is trapped in aqueous compartments
- Formulation: Particle size, salt form, enteric coating
- GI factors: Gastric emptying, intestinal motility, presence of food (fatty meals increase absorption of fat-soluble drugs like griseofulvin)
Distribution: Reversible transfer of drug between compartments after absorption.
Volume of Distribution (Vd):
- Vd = Amount of drug in body / Plasma drug concentration
- Apparent volume in which the drug distributes (does not represent a real anatomical space)
- Vd > 5 L (body water) → drug concentrates in tissues (high tissue affinity)
- Vd < 5 L → drug remains primarily in plasma (highly protein-bound or polar)
Protein Binding:
- Highly protein-bound drugs: Warfarin (99%), phenytoin (90%), thyroxine (99.5%)
- Free (unbound) drug is pharmacologically active and available for distribution/metabolism/excretion
- Displacement interactions: One drug displaces another from plasma proteins → increased free fraction of displaced drug → toxicity (e.g., warfarin + sulfonamides → bleeding)
- Hypoalbuminemia: Reduced binding capacity → increased free drug → toxicity even at normal total drug levels
Body Fluid Compartments:
- Total body water: ~42 L (60% body weight)
- Plasma: ~3 L
- Extracellular fluid: ~15 L
- Intracellular fluid: ~27 L
⚡ Exam Tip for INI CET (AIIMS PG): Vd of 40–60 L for a drug means it is extensively distributed into tissues. High Vd drugs include antidepressants, antipsychotics, antimalarials.