CardiacPBPK

CardiacPBPK predicts time-concentration profiles of drugs and one metabolite in heart tissue and venous plasma using physiologically based pharmacokinetic (PBPK) simulations to support cardiotoxicity assessment.

Key Features:

• Modular PBPK model implementation: Implements a modular PBPK model specifically for heart tissue to enable detailed cardiac compartment simulations.
• Physiologically based pharmacokinetic-quantitative system framework: Uses a physiologically based pharmacokinetic-quantitative system framework to integrate physiological and biochemical parameters.
• R and Shiny visualization: Provides interactive visualization of simulation results via the R environment and Shiny.
• Multiple administration routes: Simulates oral and intravenous dosing and predicts concentrations in venous plasma and heart tissue.
• Metabolite prediction: Predicts time-concentration profiles for the parent compound and one metabolite.
• Genetic polymorphism modeling: Supports simulation of genetic polymorphisms affecting drug metabolism, exemplified by CYP2D6.
• Modular design for customization: Modular architecture enables customization of model components for specific study requirements.

Scientific Applications:

• In-silico toxicological assessment: Assesses cardiotoxicity risk of candidate drugs by simulating cardiac exposure over time.
• Drug safety and efficacy evaluation: Supports evaluation of drug safety and efficacy through mechanistic cardiac pharmacokinetic predictions.
• Pharmacogenomic investigation: Enables study of genetic effects on cardiac drug disposition, demonstrated for amitriptyline intoxication under CYP2D6 variations.

Methodology:

Implemented as a modular physiologically based pharmacokinetic-quantitative system model in R with Shiny visualization, performing mechanistic PBPK simulations of oral and intravenous dosing to generate time-concentration profiles for parent compounds and one metabolite in venous plasma and heart tissue.