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Intravitreal Pharmacokinetics in Mice: SPECT/CT Imaging and Scaling to Rabbits and Humans

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Download Hi-Res ImageDownload to MS-PowerPointCite This:Mol. Pharmaceutics 2019, 16, 10, 4399-4404
    Brief Article

    Intravitreal Pharmacokinetics in Mice: SPECT/CT Imaging and Scaling to Rabbits and Humans
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    • Mechthild Schmitt
      Mechthild Schmitt
      Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
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    • Eero Hippeläinen
      Eero Hippeläinen
      Department of Physics, University of Helsinki, P.O. Box 64, FI-00014 Helsinki, Finland
      HUS Medical imaging Center, Clinical Physiology and Nuclear Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
      More by Eero Hippeläinen
    • Manuela Raviña
      Manuela Raviña
      Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
      More by Manuela Raviña
    • Blanca Arango-Gonzalez
      Blanca Arango-Gonzalez
      Centre for Ophthalmology, University Eye Hospital Tübingen, Tübingen, Germany
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    • Maxim Antopolsky
      Maxim Antopolsky
      Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
      More by Maxim Antopolsky
    • Kati-Sisko Vellonen
      Kati-Sisko Vellonen
      School of Pharmacy, University of Eastern Finland, Kuopio, Finland
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    • Anu J. Airaksinen
      Anu J. Airaksinen
      Department of Chemistry—Radiochemistry, University of Helsinki, Helsinki, Finland
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      Orcidhttp://orcid.org/0000-0002-5943-3105
    • Arto Urtti*
      Arto Urtti
      Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
      School of Pharmacy, University of Eastern Finland, Kuopio, Finland
      Laboratory of Biohybrid Technologies, Institute of Chemistry, St. Petersburg State University, Peterhoff, Russian Federation
      *E-mail: [email protected]. Tel: +358 40 540 2279.
      More by Arto Urtti
      Orcidhttp://orcid.org/0000-0001-6064-3102
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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2019, 16, 10, 4399–4404
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    https://doi.org/10.1021/acs.molpharmaceut.9b00679
    Published August 20, 2019
    Copyright © 2019 American Chemical Society
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    Abstract

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    Preclinical in vivo tests of retinal drug responses are carried out in mice and rats, often after intravitreal injections. However, quantitative pharmacokinetics in the mouse eye is poorly understood. Ocular pharmacokinetics studies are usually done in rabbits. We investigated elimination of three compounds ([99mTc]Tc-pentetate, [111In]In-pentetreotide, [99mTc]Tc-human serum albumin with molecular weights of 510.2 Da, 1506.4 Da, and 66.5 kDa, respectively) from mouse vitreous using imaging with single photon emission computed tomography/computed tomography (SPECT/CT). Increasing molecular weight decreased elimination of the compounds from the mouse eyes. Half-lives of [99mTc]Tc-pentetate, [111In]In-pentetreotide, and [99mTc]Tc-human serum albumin in the mouse eyes were 1.8 ± 0.5 h, 4.3 ± 1.7 h, and 30.0 ± 9.0 h, respectively. These values are 3–12-fold shorter than half-lives of similar compounds in the rabbit vitreous. Dose scaling factors were calculated for mouse-to-rabbit and mouse-to-man translation. They were 27–90 and 38–126, respectively, for intravitreal injections in rabbit and man. We show ocular pharmacokinetic parameters for mice and interspecies scaling factors that may augment ocular drug discovery and development.

    Copyright © 2019 American Chemical Society

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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2019, 16, 10, 4399–4404
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.molpharmaceut.9b00679
    Published August 20, 2019
    Copyright © 2019 American Chemical Society
    Request reuse permissions

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