Drug Distribution

Drug Distribution

Drug distribution is the reversible transfer of a drug from the systemic circulation to various tissues, organs, and body fluids of the body following its absorption, influenced by physiological and physicochemical factors such as blood flow, plasma protein binding, tissue affinity, and membrane permeability.

Factors Affecting Drug Distribution

• Blood flow: Well-perfused organs receive drugs faster.
• Plasma protein binding: Only the free (unbound) drug can distribute to tissues.
• Tissue binding: Drugs may accumulate in fat, bone, or organs.
• Lipid solubility: Lipophilic drugs distribute more widely.
• Ionization and molecular size: Non-ionized and smaller drugs cross membranes easily.
• Physiological barriers: Barriers like the blood–brain barrier limit distribution.
• Age and disease: Conditions affecting proteins or circulation alter distribution.

Volume of Distribution (Vd)

Volume of distribution is the theoretical volume of body fluid that would be required to contain the total amount of drug in the body at the same concentration as that present in plasma.

Vd
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Example:

A patient receives an IV dose of 500 mg of a drug. The initial plasma concentration is measured to be 10 mg/L. Calculate the volume of distribution.

Formula: 

Calculation: 

Loading Dose (LD)

Loading dose is the initial higher dose of a drug administered to rapidly achieve the desired therapeutic plasma concentration, especially for drugs with a long half-life.

Formula:
LD =

Example: A loading dose of digoxin is given to rapidly achieve therapeutic plasma levels in the treatment of heart failure and atrial fibrillation due to its large volume of distribution and long half-life.

Maintenance Dose (MD)

Maintenance dose is the dose of a drug administered at regular intervals to maintain the plasma drug concentration within the therapeutic range after the desired level has been achieved

Formula:

MD
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Example:

Metformin: Given as a maintenance dose (e.g., 500–1000 mg twice daily) to maintain optimal blood glucose control after initiation of therapy in type 2 diabetes mellitus.