(4) Physiologic-based Pharmacokinetic Models (PBPK)

 What are PBPK models?

Models that represent:

• REAL physiology instead of simple compartments

Difference from Compartment Models

Compartment models:

• Simplified

• 1–3 compartments

• “Blended body”

Difference from Compartment Models

PBPK models:

• Many compartments (10–20+)

• Represent:

  • Organs

  • Tissues

Why use PBPK?

👉 When you care about:

• Specific organ (e.g., kidney, liver)

👉 Because:

• Regular compartments = too simple

What PBPK includes

• Absorption

• Distribution

• Metabolism

• Excretion

👉 But in real organ-specific way

 

Complexity

• MANY compartments

• MANY rate constants

• ❗ Requires special software

PBPK

 Example

 Example: Kidney Model

• Blood flows into kidney

• Inside kidney:

  • Pre-filter region

  • Post-filter region

• Drug moves between them

• Then → urine

Partition Coefficient (P)

Definition:

 Ratio of drug in tissue vs blood

Partition Coefficient (P)

Formula (concept):

Tissue concentration / Blood concentration

Partition Coefficient (P)

What it tells you:

 How drug distributes into tissues

What affects P:

• Lipophilicity

• Ionization

• pKa

• Molecular size

• Tissue properties

Why PBPK matters clinically

• Helps predict:

  • Drug distribution

  • Organ-specific exposure

• Used in:

  • Research

  • Drug development

  • Advanced clinical modeling