The gastrointestinal tract (GIT) is the most common site for drug absorption because most medicines are taken orally. For a drug to enter the bloodstream, it must dissolve in GI fluids, cross the intestinal membrane, and reach systemic circulation. Understanding these steps helps explain why some drugs absorb quickly, some slowly, and some not at all.
What Is Drug Absorption?
Drug absorption is the movement of a drug from the site of administration (like the stomach or intestine) into the blood. Good absorption improves bioavailability and ensures the drug produces its intended therapeutic effect.
Steps Involved in GI Drug Absorption
- Disintegration: solid dosage forms break into smaller particles
- Dissolution: drug dissolves in gastric or intestinal fluids
- Penetration: dissolved drug crosses the intestinal membrane
- Entry into blood: drug reaches systemic circulation
Main Mechanisms of Drug Absorption
1. Passive Diffusion (Most Common)
Drug moves from an area of high concentration to low concentration without energy.
- Lipophilic (fat-loving) drugs diffuse easily
- Small, unionized molecules cross membranes quickly
2. Facilitated Diffusion
Uses carrier proteins but does not require energy. Works for drugs resembling natural nutrients.
3. Active Transport
Drug moves against concentration gradient using energy (ATP).
- Used by drugs similar to amino acids, sugars, or vitamins
- Carrier-specific and saturable
4. Endocytosis
Cell membrane engulfs the drug into a vesicle.
- Important for large or complex molecules
- Rare compared to other mechanisms
GI Physiology Affecting Drug Absorption
1. Gastric pH
- Stomach is acidic (pH 1–3)
- Weak acids absorb better in stomach
- Weak bases absorb better in intestine
2. Gastric Emptying Rate
- Faster emptying → faster drug reaches intestine → better absorption
- Delayed emptying slows absorption
3. Intestinal Surface Area
The small intestine has a very large surface area due to villi and microvilli, making it the main site of absorption.
4. GI Motility
- High motility → less time for absorption
- Low motility → higher absorption
5. Presence of Food
- Food may enhance or decrease absorption depending on the drug
- High-fat meals can increase absorption of lipophilic drugs
Drug-Related Factors Affecting Absorption
1. Solubility
Drugs must dissolve in GI fluids before absorption. Poorly soluble drugs absorb slowly.
2. Particle Size
Smaller particles dissolve faster, improving absorption.
3. Ionization
Unionized (non-charged) forms absorb better than ionized (charged) ones.
4. Stability in GI Fluids
- Some drugs degrade in acidic pH (e.g., penicillin G)
- Some are destroyed by digestive enzymes (e.g., insulin)
Transporters in GI Drug Absorption
1. Efflux Transporters (e.g., P-glycoprotein)
- Push drugs back into the GI lumen
- Decrease absorption
2. Uptake Transporters
- Help certain drugs enter intestinal cells
- Increase absorption
First-Pass Metabolism
Some drugs are metabolized by the intestine or liver before they reach systemic circulation. This reduces bioavailability. Example: nitroglycerin.
Special Cases Affecting Absorption
1. Slow or No Absorption
- Very hydrophilic drugs cannot cross membranes easily
- Very lipophilic drugs may remain in the membrane
2. Enteric-Coated Tablets
Protect drugs from stomach acid and release them only in the intestine.
3. Sustained-Release Formulations
- Release drug slowly over time
- Absorption depends on polymer system and GI transit
Clinical Importance
- Helps predict onset and intensity of drug action
- Guides choice of dosage form
- Explains drug-food interactions
- Important in designing controlled-release products
Detailed Notes:
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