Modeling and Simulation of Intracellular Drug Transport and Disposition Pathways with Virtual Cell
Journal Title: Journal of Pharmaceutics & Pharmacology - Year 2013, Vol 1, Issue 1
Abstract
The development of computational approaches for modeling the spatiotemporal dynamics of intracellular, small molecule drug concentrations has become an increasingly important area of pharmaceutical research. For systems pharmacology, the system dynamics of subcellular transport can be coupled to downstream pharmacological effects on biochemical pathways that impact cell structure and function. Here, we demonstrate how a widely used systems biology modeling package - Virtual Cell - can also be used to model the intracellular, passive transport pathways of small drug like molecules. Using differential equations to represent passive drug transport across cellular membranes, spatiotemporal changes in the intracellular distribution and concentrations of exogenous chemical agents in specific subcellular organelles were simulated for weakly acidic, neutral, and basic molecules, as a function of the molecules’ lipophilicity and ionization potentials. In addition, we simulated the transport properties of small molecule chemical agents in the presence of a homogenous extracellular concentration or a transcellular concentration gradient. We also simulated the effects of cell type dependent variations in the intracellular microenvironments on the distribution and accumulation of small molecule chemical agents in different organelles over time, under influx and efflux conditions. Lastly, we simulated the transcellular transport of small molecule chemical agents, in the presence of different apical and basolateral microenvironments. By incorporating existing models of drug permeation and subcellular distribution, our results indicate that Virtual Cell can provide a user-friendly, open, online computational modeling platform for systems pharmacology and biopharmaceutics research, making mathematical models and simulation results accessible to a broad community of users, without requiring advanced computer programming knowledge.
Authors and Affiliations
Gus R Rosania
Keywords
Related Articles
- EP ID EP197887
- DOI 10.13188/2327-204X.1000004
- Views 125
- Downloads 0
Modeling and Simulation of Intracellular Drug Transport and Disposition Pathways with Virtual Cell
The development of computational approaches for modeling the spatiotemporal dynamics of intracellular, small molecule drug concentrations has become an increasingly important area of pharmaceutical research. For systems...
Development of Controlled- Release Solid Dispersion Granules Containing a Poorly Water-Soluble Drug, Porous Calcium Silicate, and the Water-Soluble Polymer Polyvinylpyrrolidone
Objectives: This study sought to develop controlled-release solid dispersion granules containing a poorly water-soluble drug, porous calcium silicate (PCS), and a water-soluble polymer. Methods: Nifedipine (NIF) and ind...
Use of Intravenous Acetaminophen to Reduce Opioid Use in Patients Undergoing Bariatric Surgery at a Community Teaching Hospital
Purpose: The use of intravenous (IV) acetaminophen has been evaluated in several clinical trials and systematic reviews and has been shown to be an effective pain medication that can reduce the need for opioids. Recently...
QbD Based Approach to Design Controlled Strategy for Wet Granulation Method Using Plackett Burman Design-Case Study
Objective: The objective of present work describes developing controlled strategy for wet granulation process by identifying critical process parameters and study was done using DoE in support of Quality by Design (QbD)....
Another Example of a Successful Use of Computational and Modeling Tools from the Theory of Dynamic Systems in Pharmacokinetic Modeling
The objective of the current more or less theoretical study was to provide another example of a successful use of computational and modeling tools from the theory of dynamic systems in pharmacokinetic modeling. The tools...