Abstract

Introduction: Physiologically based pharmacokinetic (PBPK) modeling has become an important tool in modern pharmacokinetic research for predicting drug disposition and optimizing clinical study design. The aim of the present study was to evaluate the applicability of PBPK modeling for the development of a D-optimal sampling strategy for metoclopramide (MCP) after oral administration in healthy volunteers.
Materials and Methods: Eighteen healthy Caucasian male volunteers received a single oral dose of 10 mg metoclopramide.mPlasma concentrations were determined using a validated HPLC-FLD method. PBPK analysis was performed using PKQuest software. Six subjects were used for model development and twelve for validation. Model performance was evaluated using regression analysis, mean prediction error (ME), and root mean squared error (RMSE).
Results: A statistically significant correlation between predicted and observed concentrations was observed (r = 0.787, p< 0.001). ME and RMSE values demonstrated acceptable levels of bias and precision.
Discussion: The results indicate that PBPK modeling can reliably predict pharmacokinetic profiles and may be effectively applied to determine D-optimal sampling times, providing an alternative to traditional compartmental approaches.
Conclusion: PBPK modeling represents a robust and efficient tool for optimizing pharmacokinetic study design and reducing sampling burden in clinical studies.
Keywords: PBPK modeling; pharmacokinetics; D-optimal design; metoclopramide; clinical pharmacol.