Related Experiment Video
Updated: Feb 23, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Predicting Drug Concentration-Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically-Based
Yumi Yamamoto1, Pyry A Välitalo1, Dymphy R Huntjens2
1Division of Pharmacology, Cluster Systems Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Abstract:
Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically based pharmacokinetic (PBPK) model for prediction of drug concentrations in physiologically relevant CNS compartments. System-specific and drug-specific model parameters were derived from literature and in silico predictions. The model was validated using detailed concentration-time profiles from 10 drugs in rat plasma, brain extracellular fluid, 2 cerebrospinal fluid sites, and total brain tissue. These drugs, all small molecules, were selected to cover a wide range of physicochemical properties. The concentration-time profiles for these drugs were adequately predicted across the CNS compartments (symmetric mean absolute percentage error for the model prediction was <91%). In conclusion, the developed PBPK model can be used to predict temporal concentration profiles of drugs in multiple relevant CNS compartments, which we consider valuable information for efficient CNS drug development.
More Related Videos
Related Concept Videos
Pharmacokinetic Models: Comparison and Selection Criterion
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Pharmacokinetic Models: Overview
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
Model Approaches for Pharmacokinetic Data: Compartment Models
Two primary types of compartment models are recognized: mammillary and catenary. The more...
Pharmacokinetic–Pharmacodynamic Relationship: Model Components
Compartment Models: Two-Compartment Model
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion,...

