Effects of bovine serum albumin and recirculation rate on the uptake of propranolol by rat perfused lung.
Lungs isolated from 7-week-old rats were perfused with pH 7.4, oxygenated Krebs-Ringer bicarbonate buffer solution containing 2.5 micrograms mL-1 of propranolol and 3 to 5% BSA at the recirculation rate of 4 to 16 mL min-1, at 37 degrees C for 60 min. The extent of propranolol metabolism after 60 min was less than 2.3% of the initial load under any in-vitro perfusion condition. Therefore, the amount disappearing from the perfusion medium was considered as being predominantly that taken up by tissue. Under all experimental conditions, perfusate drug level declined bi-exponentially with time. Apparent in-vitro pulmonary clearance of propranolol was not affected by the increase of BSA level from 3 to 5%. When the perfusate BSA level was fixed at 3%, the lowest recirculation rate (4 mL min-1) yielded the smallest clearance (about 0.15 mL min-1 g-1) but almost constant clearance value (about 0.40 mL min-1 g-1) was obtained at the rate ranging from 8 to 16 mL min-1. The tissue to medium concentration ratio of propranolol, after the perfusion with 3 to 5% BSA at the rate of 8 to 16 mL min-1, was approximately 35, whereas that with 3% BSA at 4 mL min-1 was reduced to about 20. The findings suggest evidence for flow-dependent in-vitro pulmonary clearance of propranolol.
Iwamoto
K
K
Department of Pharmacy, Shimane Medical University Hospital, Izumo, Japan.
Watanabe
J
J
Yonekawa
H
H
D000818:Animals; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011433:Propranolol / Q000378:metabolism* / Q000493:pharmacokinetics; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
D012710:Serum Albumin, Bovine; D011433:Propranolol