Related Experiment Video
Updated: Jul 12, 2025
08:59
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
7.9K
Adult and pediatric physiologically-based biopharmaceutics modeling to explain lamotrigine immediate release
Edilainy Rizzieri Caleffi-Marchesini1, Amanda Antunes Herling1, Julia Macente1
1Pharmacokinetics and Biopharmaceutics Laboratory, State University of Maringá, Maringá, PR, Brazil.
CPT: Pharmacometrics & Systems Pharmacology
|November 2, 2023
Summary
Physiologically-based biopharmaceutics modeling assessed lamotrigine
Area of Science:
- Pharmacology
- Biopharmaceutics
- Drug Development
Background:
- Physiologically-based biopharmaceutics modeling (PBBM) aids drug and formulation development, particularly for pediatric populations with maturational pharmacokinetics.
- Lamotrigine (LTG), a Biopharmaceutics Classification System (BCS) II drug, requires biopharmaceutic risk assessment in special populations.
- Pediatric drug development necessitates understanding the impact of gastrointestinal tract (GIT) ontogeny on drug absorption.
Purpose of the Study:
- To evaluate the biopharmaceutic risk of low-solubility lamotrigine (LTG) by considering pediatric gastrointestinal tract (GIT) physiological parameter ontogeny.
- To develop and verify an oral physiologically-based pharmacokinetic (PBPK) and PBBM model for LTG in adults and children (2-12 years).
- To investigate the influence of GIT physiological parameters on LTG's in vivo dissolution and absorption.
Main Methods:
- Developed and verified an oral physiologically-based pharmacokinetic (PBPK) and PBBM model using GastroPlus™ for adults and pediatric populations (2-12 years).
- Conducted sensitivity analysis to evaluate biopharmaceutic properties and GIT physiological parameters.
- Simulated high-dose scenarios for adults (200 mg) and children (5 mg/kg, max 200 mg) to assess worst-case biopharmaceutic risks.
Main Results:
- Sensitivity analysis revealed gastric transit time as the most impactful parameter on LTG's biopharmaceutics.
- No significant interference was observed between gastrointestinal fluid volume and dose volumes affecting LTG's in vivo dissolution.
- The study proposes a hypothesis that LTG may exhibit BCS II in vitro characteristics but BCS I-like behavior in vivo.
Conclusions:
- Gastric transit time is a critical factor influencing the biopharmaceutic performance of lamotrigine (LTG) in pediatric populations.
- The developed PBBM provides a framework for model-informed precision dosing tailored to specific populations and clinical conditions.
- This modeling approach can guide the assessment of various release profiles for optimizing LTG's in vivo performance in adults and children.
More Related Videos
Related Concept Videos
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
42
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
42
01:15One-Compartment Open Model for Extravascular Administration: First-Order Absorption Model
226
The first-order absorption model for extravascular administration describes the rate at which a drug is absorbed and eliminated, following the principles of first-order kinetics. This model is vital as it provides a mathematical representation of drug behavior within the body. It also allows for the prediction and interpretation of drug absorption and elimination based on the rate of change in drug concentration over time. This model can be visualized as a plasma concentration-time profile...
226
01:15Model Approaches for Pharmacokinetic Data: Physiological Models
52
Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...
52
01:19One-Compartment Open Model for IV Bolus Administration: General Considerations
216
The one-compartment model is a pharmacokinetic tool that models the body as a single, uniform compartment, facilitating the understanding of drug distribution and elimination. This model is particularly beneficial for intravenous (IV) bolus administration, where the drug rapidly circulates throughout the body.
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
216
00:57Physiological Pharmacokinetic Models: Blood Flow-Limited Versus Diffusion-Limited Models
91
Physiological pharmacokinetic models, often called flow-limited or perfusion models, typically assume a swift drug distribution between tissue and venous blood, creating a rapid drug equilibrium. This premise is based on the idea that drug diffusion is extremely fast, and the cell membrane presents no barrier to drug permeation. In this scenario, where no drug binding occurs, the drug concentration in the tissue equals that of the venous blood leaving the tissue. This greatly simplifies the...
91
01:26Pharmacokinetic Models: Comparison and Selection Criterion
79
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
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.
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.
79