Drug distribution refers to the process by which a drug moves from the bloodstream into various tissues and organs of the body. After absorption or IV administration, the drug does not remain only in the blood—it spreads to muscles, fat, brain, liver, kidneys, and other tissues depending on its properties and physiological factors. Understanding distribution helps predict drug action, duration, and dosing adjustments.
What Is Drug Distribution?
It is the reversible transfer of a drug between the blood and body tissues. Once the drug enters systemic circulation, it travels to tissues based on blood flow, drug solubility, and binding characteristics.
Key Factors Affecting Drug Distribution
1. Blood Flow to Tissues
Tissues with high blood flow receive drugs faster:
- Highly perfused: heart, liver, kidneys, brain
- Moderately perfused: muscles
- Poorly perfused: fat, skin, adipose tissue
This explains why some drugs act quickly—because they reach vital organs rapidly.
2. Lipid Solubility of Drug
Lipophilic (fat-soluble) drugs cross cell membranes easily and enter tissues like the brain and adipose tissue. Hydrophilic (water-soluble) drugs stay mainly in blood and extracellular fluids.
3. Plasma Protein Binding
Many drugs bind to blood proteins such as:
- Albumin – binds acidic drugs (warfarin, phenytoin)
- α1-acid glycoprotein – binds basic drugs (lidocaine, propranolol)
Only the free (unbound) drug produces therapeutic effects. Highly protein-bound drugs have:
- Less free drug available
- Longer duration of action
- High risk of interactions if displaced by other drugs
4. Tissue Binding
Some drugs accumulate in tissues:
- Lipophilic drugs → fatty tissues
- Tetracyclines → bones and teeth
- Chloroquine → liver and spleen
This can prolong drug action or cause toxicity.
5. Ability to Cross Barriers
a. Blood–Brain Barrier (BBB)
- Only lipid-soluble or transporter-mediated drugs cross easily
- Protects the brain from many drugs
b. Placental Barrier
Many drugs cross the placenta and reach the fetus. Lipid-soluble and low molecular weight drugs cross more readily.
c. Blood–Testis Barrier
Restricts entry of many drugs, affecting treatment of testicular infections.
Volume of Distribution (Vd)
The volume of distribution is a theoretical volume that explains how extensively a drug is distributed in the body. It does not represent a real physical volume but indicates where the drug prefers to stay.
Formula
Vd = Amount of drug in body / Plasma concentration
Interpretation
- Low Vd (< 10 L): Drug stays mostly in blood (e.g., heparin)
- Moderate Vd (10–40 L): Drug distributes in body water (e.g., aminoglycosides)
- High Vd (> 100 L): Drug stored in tissues and fat (e.g., antidepressants)
Clinical Significance of Vd
- Helps calculate loading doses
- Explains drug accumulation in tissues
- Affects half-life—higher Vd → longer half-life
- Helps predict drug removal by dialysis
Redistribution of Drugs
Some drugs first enter organs with high blood flow (like the brain), then redisperse to fatty tissues, reducing their effect quickly. Example:
- Thiopental – causes fast anesthesia but wears off rapidly due to redistribution
Special Clinical Considerations
1. In Liver or Kidney Disease
- Low albumin levels → more free drug → higher toxicity risk
- Reduced metabolism → prolonged drug action
2. In Elderly Patients
- Less muscle mass → changes in distribution
- More fat content → lipophilic drugs accumulate
3. In Pregnancy
- Increased blood volume changes Vd
- Drugs may cross the placenta
Why Drug Distribution Matters
- Helps predict drug onset and duration
- Determines dosing frequency
- Helps in managing drug toxicity
- Explains drug–drug interactions
- Essential for therapeutic drug monitoring
Detailed Notes:
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