Propranolol uptake with high capacity by rat perfused lung

Lung isolated from 7-week-old rats was perfused with pH 7.4 Krebs-Ringer bicarbonate buffer solution (35 mL) containing 1 to 100 micrograms mL-1 of propranolol and 3% BSA at the recirculation rate of 8 mL min-1. Almost parallel bi-exponential drug concentration-time curves were obtained at the initial load lower than 10 micrograms mL-1, whereas relatively slow, mono-exponential decline was found after perfusion at 100 micrograms mL-1. Pharmacokinetic analysis for the perfusate propranolol concentration-time curves when loaded at 1 to 10 micrograms mL-1 yielded almost comparable values for the pulmonary perfusion clearance (0.387 +/- 0.092 to 0.486 +/- 0.095 mL min-1 g-1). In contrast, this parameter was significantly reduced at 100 micrograms mL-1 (0.113 +/- 0.042 mL min-1 g-1). The present findings suggest a trend towards saturation kinetics in the in-vitro pulmonary clearance of propranolol.