(4B) Physiologic-based Pharmacokinetic Models (PBPK)

 Partition Coefficient (p-value)

• Ratio of drug concentration in tissue vs blood

• Different from log P

  • log P = oil vs water (lab)

  • p-value = real body tissues

JUST LOOK!! ON FORMULA SHEET!

Partition Coefficient (p-value)

Key Concept

• Each tissue has different p-value

  • Brain ≠ Liver ≠ Lung

JUST READ:

 How to Use (EXAM)

👉 MATH

• Formula:

  • Tissue concentration = Blood concentration × p-value

➡ Professor explicitly said:

• You may get ANY previous PK math + p-value added

 Partition Coefficient (p-value)

Why this matters

• Used when targeting:

  • Brain (anxiety, epilepsy)

  • Specific infection sites (antibiotics)

 PBPK MODEL STRUCTURE

 Organs classified into:

• Eliminating organs

  • Drug leaves system (kidney, liver, etc.)

• Non-eliminating organs

PBPK MODEL STRUCTURE

Blood Flow

• Arterial → Tissue → Venous

• Exception: lungs (reverse flow)

 PBPK MODEL STRUCTURE

 Model Building

• Each organ → own equation

• All equations combined → full PK model

 PBPK MODEL STRUCTURE

 Dose Entry

• Must specify where drug enters

  • Example: oral dose → GI tract

 WHY PBPK MODELS ARE USED

• Want tissue concentrations

• Link drug concentration → effect

• Study toxicity (toxicokinetics)

• Predict across species (mouse → human)

Validation Concept

• Deconvolution:

• Convolution:

• Deconvolution: blood → predict tissues

• Convolution: tissues → predict blood