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Computational pharmacokinetic rationale for intra-arterial delivery to the brain

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Abstract

Intra-arterial (IA) drug delivery has been proposed for the treatment of a wide range of brain diseases, including malignant brain tumors. However, pharmacokinetic optimization for IA drug delivery to the brain remains a challenge. In this report, we apply and expand the well-established Dedrick model of IA drug delivery to the brain and test the effects of modifying drug and delivery parameters. These simulations show that altering the properties of candidate drugs and physiological variables can have profound effects on regional deposition after IA injections. We show that drug and physiological optimization aimed at rapid drug extraction and sustained retention is necessary to maximize regional deposition after of IA injections.

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Authors and Affiliations

  1. Department of Anesthesiology, Columbia University Medical Center, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA

    Johann N. R. Cooke & Shailendra Joshi

  2. Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA

    Jason A. Ellis & Jeffrey N. Bruce

  3. Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA

    Shaolie Hossain

  4. Institute for Computational Engineering and Sciences, University of Texas, Austin, TX, USA

    Shaolie Hossain

  5. Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

    Juliane Nguyen

Authors
  1. Johann N. R. Cooke
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  2. Jason A. Ellis
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  3. Shaolie Hossain
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  4. Juliane Nguyen
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  5. Jeffrey N. Bruce
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  6. Shailendra Joshi
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Corresponding author

Correspondence to Shailendra Joshi.

Ethics declarations

All experiments reported comply with the current laws of the USA. All experiments were approved by the Columbia University Institutional Review Board.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The study was funded by the National Cancer Institute at the National Institutes of Health RO1-CA-138643.

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Cooke, J.N.R., Ellis, J.A., Hossain, S. et al. Computational pharmacokinetic rationale for intra-arterial delivery to the brain. Drug Deliv. and Transl. Res. 6, 622–629 (2016). https://doi.org/10.1007/s13346-016-0319-6

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  • DOI: https://doi.org/10.1007/s13346-016-0319-6

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