Influence of perfusate composition on drug disposition in the in-situ perfused rat lung.
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.
Liu
Xin
X
School of Medicine, Princess Alexandra Hospital, University of Queensland, Woollongabba, Queensland 4102, Australia.
Wang
Jimmy Yujia
JY
Khlentzos
Alexander M
AM
Fontaine
Frank
F
Nikolovski
Julijana
J
Goh
Lee-Ann
LA
Roberts
Michael S
MS
D000818:Animals; D000983:Antipyrine / Q000493:pharmacokinetics; D001262:Atenolol / Q000493:pharmacokinetics; D002021:Buffers; D002250:Carbon Radioisotopes; D017666:Deuterium Oxide / Q000493:pharmacokinetics; D003911:Dextrans / Q000378:metabolism / Q000494:pharmacology*; D005070:Evans Blue / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007201:Indicator Dilution Techniques; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009025:Morpholines / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods*; D010539:Permeability; D011312:Pressure; D011433:Propranolol / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000494:pharmacology*; D013395:Sucrose / Q000493:pharmacokinetics
D002021:Buffers; D002250:Carbon Radioisotopes; D003911:Dextrans; D009025:Morpholines; C008550:morpholinopropane sulfonic acid; D012710:Serum Albumin, Bovine; D005070:Evans Blue; D001262:Atenolol; D013395:Sucrose; D011433:Propranolol; D017666:Deuterium Oxide; D000983:Antipyrine