Related Experiment Video
Updated: Jul 2, 2025
11:07
Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
Published on: November 24, 2021
2.8K
Predicting Human Dermal Drug Concentrations Using PBPK Modeling and Simulation: Clobetasol Propionate Case Study.
William W van Osdol1, Jasmina Novakovic1, Maxime Le Merdy1
1Simulations Plus, Incorporated, 42505 10th Street West, Lancaster, California, 93534, USA.
AAPS Pharmscitech
|February 17, 2024
Summary
Computational modeling accurately predicts topical drug delivery, like clobetasol-17 propionate (CP) from cream formulations. This approach aids in optimizing topical formulations by understanding skin permeation and drug concentration.
Area of Science:
- Pharmacokinetics
- Computational modeling
- Dermatology
Background:
- Quantitative in silico tools can predict dermato-pharmacokinetics of topical formulations.
- Integrating rate equations models skin permeation and systemic exchange.
- Clobetasol-17 propionate (CP) delivery from Dermovate cream was simulated.
Purpose of the Study:
- To predict the dermato-pharmacokinetics of clobetasol-17 propionate (CP) using the Transdermal Compartmental Absorption & Transit (TCAT) Model.
- To assess the sensitivity of CP dermis concentration to formulation properties and skin permeation.
- To illustrate the applicability of computational modeling in topical formulation design.
Main Methods:
- Simulated CP delivery from Dermovate cream using the TCAT Model in GastroPlus.
- Estimated model input parameters from public data and quantitative structure-permeation relationships.
- Validated model outputs against CP dermis concentration-time profiles from dermal microperfusion studies.
Main Results:
- The model reasonably predicted unbound dermis CP concentrations over time and skin depth.
- Dermis CP concentration was highly sensitive to drug solubility in the emulsion.
- Evaporative water loss and corticosteroid-induced vasoconstriction effects were also assessed.
Conclusions:
- Computational modeling accurately predicts topical drug pharmacokinetics, particularly skin permeation.
- This approach can guide the design of topical formulations by relating properties to composition and processing.
- In silico tools are valuable for optimizing topical and transdermal drug delivery systems.
![Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60445.jpg&w=3840&q=50)
Related Concept Videos
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
39
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,...
39
01:26Pharmacokinetic Models: Comparison and Selection Criterion
73
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.
73
01:13Physiological Pharmacokinetic Models: Assumption with Protein Binding
45
Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
45
01:12Analysis of Population Pharmacokinetic Data
256
Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
256
01:20Pharmacokinetic Models: Overview
687
Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
687
01:06Three-Compartment Open Model
217
The three-compartment open model is a pharmacokinetic model used to describe the distribution and elimination of drugs following extravascular administration. It comprises a central compartment representing the plasma and two peripheral compartments. The highly perfused peripheral compartment represents organs and tissues with a rich blood supply, such as the liver, kidneys, and lungs. The scarcely perfused peripheral compartment represents tissues with lower blood supply, such as adipose...
217