Distribution Parameters

Distribution Parameters

Figure 1 below shows the distribution parameters of Aspirin

Plasma Protein Binding (PPB)

• Importance: Drugs can bind to proteins in the blood plasma (like albumin). Only the "unbound" fraction of a drug is free to exert its therapeutic effect. High binding means less free drug is available.

• Desirable Range: < 90% is often preferred. Very high binding (>99%) can be problematic, as small changes in binding can lead to large changes in free drug concentration.

• Aspirin: Predicted to be a good PPB binder.

Volume of Distribution (Vd)

• Definition: Theoretical volume required to contain the total amount of drug at the same concentration observed in plasma.

• Importance: Indicates the extent of tissue distribution. Higher Vd suggests greater distribution into tissues.

• Expected Range: Vd expected range is 0.2 -20 L/Kg. Aspirin has a Vd of approximately 0.148 L/kg, indicating limited distribution (Figure 1).

Blood-Brain Barrier (BBB) Permeability

• Definition: Prediction of a compound's ability to cross the blood-brain barrier.

• Importance: Critical for CNS-targeted drugs (desirable) and non-CNS drugs (undesirable to minimize side effects). Aspirin has poor BBB permeability.

Fraction Unbound in Plasma (fu)

• Definition: Percentage of drug not bound to plasma proteins.

• Importance: Only the unbound drug is pharmacologically active. High protein binding may affect drug interactions and efficacy.

• Expected Range: Optimal range varies by therapeutic intent. Aspirin is highly protein-bound (fu ≈ 40.1 %), which contributes to its long half-life.