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 123
- Downloads 0
Invitro and Invivo Inhibition of Metyrapone metabolism by Glycyrrhetinic Acid in Male Wistar Rats
Objectives: We investigated the inhibitory effect of glycyrrhetinic acid (GA), an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, on the reductive metabolism of metyrapone (MP) in an invitro study, and the...
Current Medication Trends and Global Impact on Neurodegenerative Disorders
Neurodegenerative disorders are the medical condition characterized by destruction in neuronal cells, abruption of neuronal activity and distinct involvement of the functional movement. The main neuronal disorders like P...
Anti-Proliferative and Pro-Apoptotic Effects of (-)-Epigallocatechin-3- Gallate Encapsulated in Chitosan Nanoparticles on Human Prostate Carcinoma Cells
(-)-epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, has shown excellent effects in preventing, as well as treating, many cancers including prostate cancer (PCa) in preclinical model systems. However...
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)....
Eribis Peptide 94 Mimics Ischemic Preconditioning in Rats with an Acute Myocardial Infarction and has Cardioprotective Effects during Prolonged Ischemia
Objectives: Previously, we demonstrated that a novel enkephalin analogue, Eribis Peptide 94 (EP94), produces a reduction of myocardial infarct size in rats and pigs administrated during occlusion. Since a complete dose-r...