Factors Affecting Drug Absorption

Overview

Drug absorption is the process by which a drug moves from its site of administration into the bloodstream. Various physiological and drug-related factors influence this process, affecting a drug's effectiveness and onset of action.

Factors Influencing Drug Absorption

1. Physicochemical Properties of the Drug

- Solubility: Lipid-soluble drugs are generally absorbed faster, while water-soluble drugs may require transport mechanisms.

- Molecular Size: Smaller molecules are more easily absorbed; large molecules may need active transport.

- Ionization: Non-ionized forms are absorbed more readily as they cross cell membranes more effectively. pH affects drug ionization and absorption.

2. Route of Administration

- Oral Route: Absorption in the gastrointestinal tract is affected by gastric emptying rate and food presence.

- Parenteral Route: Bypasses absorption barriers, enabling rapid and complete absorption.

- Topical or Transdermal: Depends on skin integrity and the drugs lipid solubility.

3. Blood Flow to the Absorption Site

Higher blood flow maintains a concentration gradient, increasing absorption. Drugs injected in vascularized areas absorb faster than in fatty tissues.

4. Surface Area of the Absorption Site

A larger surface area, like that of the small intestine, promotes faster and more efficient drug absorption.

5. Gastric Emptying and Intestinal Transit Time

- Gastric Emptying: Delays in emptying slow drug absorption, influenced by food, stress, and medications.

- Intestinal Transit Time: Sufficient time in the intestine is crucial for optimal absorption. Rapid transit can reduce absorption.

6. pH and pKa of the Drug

pH varies across the GI tract, affecting the drugs ionization state. The drugs pKa determines its ionization in different pH environments, influencing absorption.

7. Presence of Food and Other Substances

- Food: Can delay, enhance, or inhibit absorption. Fatty foods can increase absorption of lipophilic drugs.

- Other Substances: Certain ions (e.g., calcium) can complex with drugs, reducing absorption.

8. Disease States

- Gastrointestinal Disorders: Conditions like Crohns disease, diarrhea, and gastric ulcers impair absorption.

- Liver Disease: May affect metabolism and first-pass effect, altering bioavailability.

9. First-Pass Metabolism

Drugs absorbed from the GI tract may undergo liver metabolism before reaching circulation, reducing bioavailability. This is bypassed by parenteral routes.

10. Interaction with Other Drugs

Certain drugs can alter GI motility, pH, or enzyme activity, affecting the absorption of co-administered drugs.