Physiological Models (PBPK – Physiologically Based Pharmacokinetic Models)

• Physiological Models (PBPK Physiologically Based Pharmacokinetic Models) predict drug ADME using organ physiology and blood flow data.

Physiological Models (PBPK – Physiologically Based Pharmacokinetic Models)

• Physiological models, or PBPK models, are the most detailed pharmacokinetic models as they incorporate actual physiological and anatomical data.

Key Features of PBPK Models:

• Based on real organ and tissue compartments (liver, kidney, brain, etc.).
• Uses blood flow rates, tissue volumes, and enzyme kinetics to predict drug behavior.
• Requires extensive physiological and biochemical data for accurate predictions.
• Simulations can be performed for different populations (children, elderly, diseased states).
  

Types of PBPK Models

1. Blood Flow-Limited Model

   • Drug distribution depends on blood flow rate and concentration gradient between blood and tissues.
   • Used for drugs with high affinity for highly perfused organs (liver, kidney, brain).
   • Helps predict tissue drug concentrations and optimize dosing.

2. Membrane Permeation-Limited Model

   • Drug distribution depends on membrane permeability (e.g., blood-brain barrier).
   • Used for low-permeability drugs or those requiring active transport.
   • Helps in designing prodrugs or nanocarriers for better absorption.

Applications of PBPK Models:

• Drug development and regulatory approval (FDA, EMA use PBPK for drug evaluation).
• Predicting drug-drug interactions (DDIs).
• Personalized medicine (dosing adjustments for individuals).

Advantages of PBPK Models:

• Provides the most realistic prediction of drug kinetics.
• Can be used to extrapolate data between species (e.g., from animals to humans).
• Allows prediction of organ-specific drug concentrations.

Disadvantages of PBPK Models:

• Highly complex and requires extensive data.
• Computationally intensive.
• Not always practical for routine clinical use.

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