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Physiologically-Based Pharmacokinetics

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Biosimulation in Biomedical Research, Health Care and Drug Development

Abstract

External control of tissues and cells, by hormones, nerves, and other stimuli, involves the transduction of signals from ligand-activated receptors to control of rate-limiting enzymes or proteins that affect key steps in metabolism, gene transcription or other processes within the cells. The signal transduction is carried out by a network of interacting signal mediators, i.e. proteins and small molecule transducers. Such signaling transduction networks display a high degree of complexity, which is due to the presence of feed-forward and feedback loops, both negative and positive, and to the fact that interactions change over time and according to intracellular location. In combination with multiple layers of control, redundancy, shared signal mediators, shared signal paths, and cross-talk between signals, this leads to a complexity that poses new challenges to progress in dissecting and understanding cellular control. Furthermore, many diseases, such as cancer, insulin resistance, and type 2 diabetes, are associated with malfunctioning in the complex signaling networks.

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Acknowledgements

The authors wish to thank all colleagues at Simcyp Limited for useful comments and acknowledge assistance of Mr James Kay with preparation of the references.

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Authors and Affiliations

  1. Simcyp Limited, Blades Enterprise Centre, John Street, Sheffield, S2 4SU, UK

    Masoud Jamei, Karen R. Yeo, Cyrus Ghobadi, Manoranjenni Chetty, Khaled Abduljalil & Gaohua Lu

  2. Simcyp Limited, Blades Enterprise Centre, John Street, S2 4SU, Sheffield, UK

    Trevor N. Johnson

  3. School of Pharmacy and Pharmaceutical Sciences, Faculty of Medical and Human Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, UK

    Farzaneh Salem, Adam Darwich & Amin Rostami-Hodjegan

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  1. Masoud Jamei
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  2. Karen R. Yeo
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  3. Trevor N. Johnson
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  10. Amin Rostami-Hodjegan
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Correspondence to Amin Rostami-Hodjegan .

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Editors and Affiliations

  1. , Department of Physics, Technical University of Denmark, Fysikvej Building 309, Kongens Lyngby, 2800, Denmark

    Erik Mosekilde

  2. , Department of Biomedical Sciences, Copenhagen University, Panum Institute, Copenhagen N, 2200, Denmark

    Olga Sosnovtseva

  3. , School of Pharmacy and Pharmaceutical Sc, University of Manchester, Oxford Road, Manchester, M13 9PT, U, United Kingdom

    Amin Rostami-Hodjegan

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Jamei, M. et al. (2011). Physiologically-Based Pharmacokinetics. In: Mosekilde, E., Sosnovtseva, O., Rostami-Hodjegan, A. (eds) Biosimulation in Biomedical Research, Health Care and Drug Development. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0418-7_16

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