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Species Similarities and Differences in Pharmacokinetics and Distribution of Antiretroviral Drugs

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Humanized Mice for HIV Research

Abstract

As with all xenobiotics, there are numerous factors that influence the pharmacokinetics and distribution of antiretroviral drugs. These include proteins involved in phase I metabolism, phase II metabolism, drug influx transport, drug efflux transport and the ligand-activated transcription factors that regulate them. The key differences between human and murine proteins responsible for the metabolism of antiretroviral drugs are discussed in this chapter. It is essential to consider species differences in metabolic enzymes, transporters and nuclear receptors when interpreting pharmacokinetic and drug–drug interaction (via induction or inhibition) data from rodent models. However, differences in tissue size and blood flow are also likely to affect disposition and must be considered when interpreting data from murine models. Mice transplanted with human hepatocytes have been shown to display a more human-like metabolic response to drugs and represent an interesting avenue for future research.

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  1. Department of Molecular and Clinical Pharmacology, University of Liverpool, 70 Pembroke Place, L69 3GF, Liverpool, UK

    Andrew Owen & Paul Curley

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  1. Andrew Owen
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Correspondence to Andrew Owen .

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Editors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA

    Larisa Y. Poluektova

  2. Center for AIDS Research, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    J. Victor Garcia

  3. Research Center for AIDS Laboratory of Viral Pathogenesis, Kyoto University Institute for Virus Research, Sakyo-ku, Japan

    Yoshio Koyanagi

  4. Division of Hematology, University Hospital Zürich, Zürich, Switzerland

    Markus G. Manz

  5. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

    Andrew M. Tager

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Owen, A., Curley, P. (2014). Species Similarities and Differences in Pharmacokinetics and Distribution of Antiretroviral Drugs. In: Poluektova, L., Garcia, J., Koyanagi, Y., Manz, M., Tager, A. (eds) Humanized Mice for HIV Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1655-9_28

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