Pharmaceutical research · 2000
An isolated in-situ rat head perfusion model for pharmacokinetic studies.
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Foster K A, Mellick G D, Weiss M, Roberts M S
Аннотация
PURPOSE: To develop a viable, single pass rat head perfusion model useful for pharmacokinetic studies.
METHODS: A viable rat head preparation, perfused with MOPS-buffered Ringer's solution, was developed. Radiolabelled markers (red blood cells, water and sucrose) were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 minutes. The double inverse Gaussian function was used to estimate the statistical moments of the markers.
RESULTS: The viability of the perfusion was up to one hour, with optimal perfusate being 2% bovine serum albumin at 37 degrees C, pH 7.4. The distribution volumes for red blood cells, sucrose and water (from all studies, n = 18) were 1.0 +/- 0.3 ml, 6.4 +/- 4.2 ml and 18.3 +/- 11.9 ml, respectively. A high normalised variance for red blood cells (3.1 +/- 2.0) suggests a marked vascular heterogeneity. A higher normalised variance for water (6.4 +/- 3.3) is consistent with additional diffusive/permeability limitations.
CONCLUSIONS: Analysis of the physiological parameters derived from the moments suggested that the kinetics of the markers were consistent with distribution throughout the head (weight 25 g) rather than just the brain (weight 2 g). This model should assist in studying solute pharmacokinetics in the head.
METHODS: A viable rat head preparation, perfused with MOPS-buffered Ringer's solution, was developed. Radiolabelled markers (red blood cells, water and sucrose) were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 minutes. The double inverse Gaussian function was used to estimate the statistical moments of the markers.
RESULTS: The viability of the perfusion was up to one hour, with optimal perfusate being 2% bovine serum albumin at 37 degrees C, pH 7.4. The distribution volumes for red blood cells, sucrose and water (from all studies, n = 18) were 1.0 +/- 0.3 ml, 6.4 +/- 4.2 ml and 18.3 +/- 11.9 ml, respectively. A high normalised variance for red blood cells (3.1 +/- 2.0) suggests a marked vascular heterogeneity. A higher normalised variance for water (6.4 +/- 3.3) is consistent with additional diffusive/permeability limitations.
CONCLUSIONS: Analysis of the physiological parameters derived from the moments suggested that the kinetics of the markers were consistent with distribution throughout the head (weight 25 g) rather than just the brain (weight 2 g). This model should assist in studying solute pharmacokinetics in the head.