Introduction to Drug Absorption

• Definition: Drug absorption is the process by which a drug enters the bloodstream from its site of administration.
• Movement: Involves the transfer of an unmetabolised drug from the administration site to the circulatory system.
• Bioavailability: Refers to the portion of the administered drug dose that reaches the systemic circulation in an unchanged form.
• Importance: Understanding drug absorption is essential for determining appropriate dosing regimens and achieving the desired therapeutic effects.

Factors Influencing Drug Absorption

1. Physicochemical Properties of the Drug

   • Solubility: Drugs must dissolve in solution to be absorbed; solid forms like tablets need to disintegrate and dissolve first.
   • Lipid Solubility: Lipophilic (fat-soluble) drugs cross cell membranes more easily than hydrophilic (water-soluble) drugs.
   • Molecular Size: Smaller molecules penetrate membranes faster than larger ones.
   • Degree of Ionisation: The un-ionised form of a drug is more lipid-soluble and thus more readily absorbed. The ratio of ionised to un-ionised drug depends on the environmental pH and the drug’s pKa (acid dissociation constant).

2. Formulation of the Drug

   • Dosage Form: The form of the drug (e.g., tablets, capsules, solutions) affects the rate of dissolution, which can be the rate-limiting step in absorption.
   • Excipients: Inactive ingredients in the formulation can impact disintegration, dissolution, and absorption.
   • Controlled-Release Formulations: Designed to slow absorption and prolong the drug’s action.

3. Route of Administration

   • Intravenous (IV): Provides direct entry into systemic circulation, bypassing absorption barriers.
   • Intramuscular (IM) or Subcutaneous (SC): Requires absorption across capillary membranes or via the lymphatic system.
   • Oral: Influenced by:
     • Gastrointestinal (GI) pH: Varies along the GI tract, affecting drug ionisation and absorption.
     • Gastric Emptying Rate: Impacts the amount of drug reaching the small intestine for absorption.
     • Food Intake: Can either enhance or inhibit absorption depending on the drug.
     • Surface Area: The small intestine has a larger surface area for absorption compared to the stomach.
     • Blood Flow: Reduced blood flow can decrease the concentration gradient and slow absorption.
     • First-Pass Metabolism: Drugs absorbed from the GI tract pass through the liver first, where they may be metabolised before reaching systemic circulation, thus reducing bioavailability.
   • Other Routes: Include buccal, sublingual, rectal, topical, transdermal, and inhaled, each with specific absorption characteristics.

4. Physiological Factors

   • Age: Absorption can be altered in infants and the elderly due to physiological differences.
   • Gastric Emptying Time: Delays or accelerations in gastric emptying can affect absorption.
   • Gastrointestinal Motility: Influences the time available for drug absorption in various parts of the GI tract.
   • Blood Flow to Absorption Site: Increased blood flow generally enhances absorption.
   • Disease States: Conditions affecting the GI tract, liver, or circulatory system can alter drug absorption.

Mechanisms of Drug Absorption

• Passive Diffusion: The movement of drug molecules from an area of high concentration to an area of low concentration; mainly used by lipophilic drugs.
• Facilitated Passive Diffusion: Carrier-mediated transport down the concentration gradient; does not require energy.
• Active Transport: Carrier-mediated transport against the concentration gradient; requires energy (ATP).
• Pinocytosis: Involves the engulfment of fluid or particles by the cell membrane to form vesicles; less common for most drugs.

Conclusion

Understanding the factors that influence drug absorption is crucial for pharmacists and healthcare providers to optimise drug therapy and achieve the desired therapeutic outcomes for patients.

References

1. Smith, J., & Brown, L. (2022). Factors affecting drug absorption and its implications in clinical practice. Clinical Pharmacokinetics, 24(3), 221-230. Retrieved from ScienceDirect
2. News-Medical. (n.d.). What is Drug Absorption?. Retrieved from News-Medical
3. University of Florida. (n.d.). What Factors Within the Body Affect Drug Absorption?. Distance Physiology. Retrieved from UF Distance Physiology
4. MSD Manual. (n.d.). Drug Absorption. Retrieved from MSD Manual