2.1 Absorption (ADME)
Absorption is the process by which a drug enters the systemic circulation from its site of administration. Understanding absorption is crucial for predicting bioavailability.
Routes of Administration
Oral (PO)
Most common. Convenient but variable absorption. First-pass metabolism in liver.
Intravenous (IV)
100% bioavailability. Immediate effect. Requires sterility, injection.
Intramuscular (IM)
Depot effect possible. Faster than oral, slower than IV.
Subcutaneous (SC)
Slow, sustained absorption. Common for biologics (insulin, antibodies).
Transdermal
Patches for sustained delivery. Avoid first-pass. Limited to lipophilic drugs.
Mechanisms of Absorption
Passive Diffusion
Most common. Down concentration gradient. Favors lipophilic, unionized drugs.
Facilitated Diffusion
Carrier-mediated, no energy. Saturable. Glucose transporters.
Active Transport
Energy-dependent. Against gradient. P-gp, OATP, OCT transporters.
Endocytosis
Pinocytosis, receptor-mediated. Important for large molecules.
Bioavailability
\( F = \frac{AUC_{oral}}{AUC_{IV}} \times \frac{Dose_{IV}}{Dose_{oral}} \)
F = fraction of dose reaching systemic circulation
Factors Reducing Bioavailability
- • First-pass metabolism (liver, gut wall)
- • P-glycoprotein efflux
- • Poor dissolution/solubility
- • Degradation in GI tract
Henderson-Hasselbalch Equation
\( pH - pK_a = \log \frac{[A^-]}{[HA]} \)
Drug ionization affects absorption: unionized form crosses membranes better. Weak acids absorbed in stomach (low pH), weak bases in intestine (higher pH).