Influence of perfusate composition on drug disposition in the in-situ perfused rat lung

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 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 cmH 2O), 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.