Development and Validation of a Chinese Obesity-Specific Physiological Database for PBPK Modeling.

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Population Modeling
• Obesity Research

Background:

• Physiologically based pharmacokinetic (PBPK) models are crucial for predicting drug behavior in specific populations.
• Existing population databases may not accurately represent the unique physiological characteristics of Chinese adults and individuals with obesity.

Purpose of the Study:

• To develop and validate a PBPK population model tailored for the Chinese obese population.
• To compare the predictive accuracy of this new model against existing East Asian and White obese population databases.

Main Methods:

• Established a Chinese adult population database in PK-Sim by recalibrating an East Asian database with new Chinese anatomical and physiological data.
• Developed and validated PBPK models for dexmedetomidine, omeprazole, and propofol using Chinese obese population data.
• Created a Chinese obese adult database by adjusting physiological parameters based on Chinese patient data and literature.

Main Results:

• All drug models were validated, with predicted Cmax and AUC values within 0.5-2 fold of observed values.
• The Chinese adult database demonstrated superior accuracy (90% AUC, 80% Cmax within 0.8-1.25 fold) compared to the East Asian database (75% AUC, 70% Cmax).
• The Chinese obese database significantly outperformed the White obese database (83% AUC, 33% Cmax vs. 33% AUC, 0% Cmax within 0.8-1.25 fold).

Conclusions:

• The validated PBPK models and the developed Chinese adult and obese adult databases reliably predict drug concentrations in these populations.
• The new Chinese-specific models offer improved accuracy over existing East Asian and White obese population databases for drug concentration prediction.