Influence of perfusate composition on drug disposition in the in-situ perfused rat lung
Date
2009
Authors
Liu, X.
Wang, J.Y.
Khlentzos, A.M.
Fontaine, F.
Nikolovski, J.
Goh, L.A.
Roberts, M.S.
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Journal article
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International Journal of Pharmaceutics, 2009; 382(1-2):192-197
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Abstract
This study compared the impact of two perfusates (A: 4.5% BSA-MOPS buffer and B: 4% dextran and 0.5% BSA-MOPS buffer) on the pharmacokinetics of the physiological markers [3H]-water, [14C]-sucrose, [14C]-antipyrine and Evans Blue-labelled albumin; and the drugs atenolol and propranolol using an insitu single pass perfusion model in the rat lung. The multiple indicator dilution approach was used to define disposition. Similar perfusion pressures (17.6±6.71 vs 17.7±8.87cmH2O), lung wet/dry ratio (6.14±1.16 vs 5.16±0.87), physiological spaces, and permeability-surface area products were found for the two perfusates. However, the recovery of propranolol using perfusate A (49.3±10.1%) was significantly higher than that using perfusate B (38.9±9.91%). This difference was consistent with changes in perfusate oncotic pressure associated with water and albumin distribution between the vascular, interstitial and cellular volumes of the lung. Copyright 2009 Elsevier B.V. All rights reserved.
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Data source: Figures & tables, https://doi.org/10.1016/j.ijpharm.2009.08.028
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Copyright 2009 Elsevier BV