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Modeling Drug Biodistribution: Cyclosporine A in Rats and Humans

This paper presents an advanced study on the biodistribution of Cyclosporine A through a closed vasculature multicompartmental model. The model allows for the accurate simulation of novel drug delivery across interconnected organs in mammalian bodies. We compare two approaches to solve the network and kinetic inversion challenge: numerically solving differential-algebraic equations (DAEs) and utilizing partial differential equations (PDEs). A case study is included, focusing on IV bolus injections in Sprague Dawley rats, highlighting the variances in absorption and distribution in humans.

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Modeling Drug Biodistribution: Cyclosporine A in Rats and Humans

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Presentation Transcript

  1. 10/14/2010 Andrej Mosat, LPPD, UIC Research update

  2. Cyclosporine A Paper • 1. Paper for Journal of Theoretical Biology on Cyclosporine A delivery in a Rat and a Human

  3. Main Points • 1. All organs in a mammalian body are interconnected. Closed vasculature multicompartmental model of arbitrary complexity can simulate novel drug's biodistribution reliably • 2. Simple first order model as a set of partial differential equations leads to more insight than complicated models with curve fitting. • 3. A case study supporting the two solution approaches will be presented on Cyclosporine A IV bolus injection in Sprague Dawley rats.

  4. Methods • We show two solution approaches to the network and kinetic inversion problem: • a.) numerically solving a networked system of DAEs by "DASSL" • b.) numerically solving the system of PDE`s by "the sensitivity method“ • - automatic equation generator • - DAE solver • - Analytical solution for systems of DAEs cannot be obtained in general

  5. Case study • Rat, bolus IV Injection vs. • Human, bolus IV Injection Challenges: Unclear measurement data. Tail ? Different Proteins in Rats/Humans

  6. Figures

  7. Rat network = Human network

  8. First principle models

  9. Concentration Profiles Rat/Human

  10. Mass balance "R:\matlab\from Eric\Cyclosporin A\20101030-FIG-CyA-Mass.jpg"

  11. Blood/Plasma "R:\matlab\from Eric\Cyclosporin A\20101030-FIG-CyA-Mass.jpg"

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