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Int J Pharm ; 382(1-2): 192-7, 2009 Dec 01.
Article in English | MEDLINE | ID: mdl-19716867

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 [(3)H]-water, [(14)C]-sucrose, [(14)C]-antipyrine and Evans Blue-labelled albumin; and the drugs atenolol and propranolol using an in-situ 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+/-8.87 cm H(2)O), 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.


Subject(s)
Dextrans/pharmacology , Indicator Dilution Techniques , Lung/drug effects , Morpholines/pharmacology , Perfusion/methods , Serum Albumin, Bovine/pharmacology , Animals , Antipyrine/pharmacokinetics , Atenolol/pharmacokinetics , Buffers , Carbon Radioisotopes , Deuterium Oxide/pharmacokinetics , Dextrans/metabolism , Evans Blue/pharmacokinetics , Hydrogen-Ion Concentration , Lung/blood supply , Lung/metabolism , Male , Models, Biological , Morpholines/metabolism , Permeability , Pressure , Propranolol/pharmacokinetics , Rats , Rats, Wistar , Serum Albumin, Bovine/metabolism , Sucrose/pharmacokinetics
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