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An Isolated In-Situ Rat Head Perfusion Model for Pharmacokinetic Studies

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Abstract

Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies.

Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers.

Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations.

Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.

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Authors and Affiliations

  1. Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Queensland, 4102, Australia

    Kelley A. Foster & George D. Mellick

  2. Section of Pharmacokinetics, Department of Pharmacology, Martin Luther University, Halle-Wittenberg, 06112, Germany

    Michael Weiss

  3. Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Queensland, 4102, Australia

    Michael S. Roberts

Authors
  1. Kelley A. Foster
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  2. George D. Mellick
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  3. Michael Weiss
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  4. Michael S. Roberts
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Foster, K.A., Mellick, G.D., Weiss, M. et al. An Isolated In-Situ Rat Head Perfusion Model for Pharmacokinetic Studies. Pharm Res 17, 127–134 (2000). https://doi.org/10.1023/A:1007500910566

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