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Project 1 - Modelling Dose Response Time Relationships

ESR - Robert Andersson

Aims

To address the novel development and application of mechanism-based models for capturing dose-response time-data when systematic exposure is lacking in current pharmacological experiments, addressing effectively for the first time the characterisation of dose response data, leading to optimisation of subsequent (pre) clinical protocols, and identifying inter-individual differences.

Supervisor: Johan Gabrielsson (SUAS), Mats Jurstrand (FCC)

Co-Supervisors: Mike Chappell (University of Warwick), Neil Evans (University of Warwick), Lambertus A. Peletier (Leiden University)

Project Objectives

  • Analyse a series of dose-response data sets orginiating from local (e.g. pulmonary) and systemic (e.g. oral) administration.
  • Development and application of mechanism-based models for capturing dose-response time-data when systemic exposure is lacking in pharmacological experiments.
  • Characterise the dose-response-time characteristics (signature profiles) and apply new methodology focussing on practical experimental designs and parameter idenitifiability issues.

Project Update

To be added.

Publications

  • Andersson, R., Gabrielsson, J., Almquist, J., Jirstand, M., Oakes, N., Evans, N.D., Chappell, M.J. & Kroon, T. ‘Modelling of free fatty acid dynamics: Insulin and NiAc resistance under acute and chronic treatments.’ Journal of Pharmacokinetics and Pharmacodynamics. In press January 2017.
  • Andersson, R., Jirstrand, M., Peletier, L.A., Chappell, M.J., Evans, N.D. & Gabrielsson, J. (2014), “Dose-response-time modelling – Second-generation turnover model with integral feedback control”. European Journal of Pharmaceutical Sciences January 2016. (doi:10.1016/j.ejps.2015.10.018)

Conference Papers

  • 5th-7th September 2016: Quantitative Systems Pharmacology UK 1st Exchange Workshop, Surrey UK. Oral Presentation.

Poster Presentations

  • 7th-10th June 2016: Population Approach Group in Europe (PAGE), Lisbon, Portugal, scientific poster presented.
  • 2nd-5th June 2015: 24th Population Approach Group in Europe (PAGE) meeting, Crete, Greece. Scientific poster presented.
  • 5th-7th November 2014: Pharmacokinetics UK (PKUK) Bath. Scientific poster presented.
  • 23rd-25th April 2014: 7th Noordwijkerhout Symposium on Pharmacokinetics, Pharmacodynamics and Systems Pharmacology, Systems Pharmacology in Drug Discovery and Development, The Netherlands. Poster presentation entitled "Dose-response-time modelling, input estimation and structural identifiability as tools for systems pharmacology"
  • 3rd-4th December 2013: Modelling and Simulation Symposium AstraZeneca Alderley Park, UK. Poster Presentation entitled “Dose-response-time data analysis”.
  • 30th October - 1st November 2013: Pharmacokinetics UK (PKUK) Harrogate, UK. Poster presentation entitled “Dose-response-time data analysis”.



Other Presentations

  • 31st May 2016: Presented research results to a group meeting at Fraunhofer-Chalmers Centre.
  • 9th March 2015: Presented research results at School of Engineering Postgraduate Symposium.
  • 20th May 2014: Presented to the Modelling and Simulation Group at AstraZeneca, Mölndal, Sweden.


Conferences Attended

    • 5th-7th September 2016: Quantitative Systems Pharmacology UK 1st Exchange Workshop, Surrey UK.
    • 7th-10th June 2016: 25th Population Approach Group in Europe meeting in Lisbon, Portugal.
    • 2nd-5th June 2015: 24th Population Approach Group in Europe meeting, Crete, Greece.
    • 5th-7th November 2014: Pharmacokinetics UK (PKUK) Bath, UK.
    • 15th-19th June 2014: 9th European Conference on Mathematical and Theoretical Biology, Gothenburg, Sweden.
    • 23rd-25th April 2014: 7th Noordwijkerhout Symposium on Pharmacokinetics, Pharmacodynamics and Systems Pharmacology, Noordwijkerhout, The Netherlands.
    • 3rd-4th December 2013: Modelling and Simulation Symposium AstraZeneca Alderley Park, UK.
    • 30th October - 1st November 2013: Pharmacokinetics UK (PKUK) Harrogate, UK.