Characterization of the physiological spaces and distribution of tolbutamide in the perfused rat pancreas

Fanning, Kent John and Roberts, Michael S. (2007) Characterization of the physiological spaces and distribution of tolbutamide in the perfused rat pancreas. Pharmaceutical Research, 24 3: 512-520. doi:10.1007/s11095-006-9167-2


Author Fanning, Kent John
Roberts, Michael S.
Title Characterization of the physiological spaces and distribution of tolbutamide in the perfused rat pancreas
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
Publication date 2007
Sub-type Article (original research)
DOI 10.1007/s11095-006-9167-2
Volume 24
Issue 3
Start page 512
End page 520
Total pages 9
Editor Lee, V. L. H.
Place of publication United States
Publisher Springer New York
Collection year 2008
Language eng
Subject C1
730199 Clinical health not specific to particular organs, diseases and conditions
Formatted abstract
Purpose To set up and validate a viable perfused rat pancreas model suitable for pharmacokinetic studies.
Materials and methods We setup and conducted multiple indicator dilution studies in the single pass perfused rat pancreas. The distribution of the reference markers [99mTc]-red blood cells (RBC), [14C]-sucrose, and [3H]-water, and tolbutamide were analysed using both non-parametric and parametric methods.
Results The perfusion preparation was observed to be viable by oxygen consumption, outflow perfusate pH, lactate release and insulin release in response to glucose. Parametric analysis of the outflow profiles suggested that the transport of water and tolbutamide from the vascular space was permeability limited. Parametric and nonparametric estimates of V d for RBC and sucrose were similar and were 0.14 ± 0.01, 0.15 ± 0.005 and 0.35 ± 0.01 ml/g. The parametric estimate for water, 1.04 ± 0.05 ml/g was greater than the nonparametric estimate, 0.89 ± 0.02 ml/g. The multiple indicator dilution method V d of tolbutamide of 0.75 ± 0.08 ml/g was similar to the reported value of 0.73 ± 0.04 ml/g estimated by tissue partitioning studies.
Conclusions A viable single pass pancreas perfusion model was established and applied to define distribution spaces of reference markers and the distribution kinetics of tolbutamide.

Keyword Chemistry, Multidisciplinary
Pharmacology & Pharmacy
distribution kinetics
pancreas perfusion
pharmacokinetics
physiological spaces
tolbutamide
Amino-acid-transport
Insulin-secretion
Physicochemical Parameters
Transcapillary Exchange
Disposition Kinetics
Hepatic Disposition
Cytoplasmic-binding
Tissue Distribution
Exocrine Pancreas
Protein-content
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Mon, 18 Feb 2008, 16:21:33 EST