Specific Age-dependence in Capacity-limited Uptake of Propranolol by Isolated Rat Lung

Abstract

Abstract To investigate the effect of age on the pulmonary uptake of propranolol, minced tissue (0·4 g) of lungs isolated from 3- to 104-week-old rats was incubated with the drug (1 to 500 ng μL−1) prepared in oxygenated, pH 7·4 Krebs-Ringer bicarbonate buffer solution (20 mL) containing 3% BS A for 60 min at 37°C. In any age-group the metabolism of propranolol was not significant (i.e. less than 0·6% of any initial load) under the present in-vitro conditions. The extent of uptake after the incubation with 2·5 μ mL−1 of the drug was largest in the 7 weeks (i.e. 82% of the initial load) and relatively small in the 3(64%), 24(61 %), 52(51%) and 104(48%) week old rats. Similar, specific age-dependence was observed in the tissue-to-medium concentration ratio of the drug. In any age-group, the initial uptake rate obtained in the first 5 min of the incubation was found to be a combination of apparently linear transport and saturable (capacity-limited) processes. There was a marked, specific age-dependence in the capacity-limited uptake rate. Although Km′ value was almost equivalent in any age-group (i.e. 24·4 to 25·4 μg mL1), Vmax exhibited a specific age-dependence by yielding the highest value in 7 weeks (0·726 ± 0·101 mg g−1 min−1) and relatively low values in 3 (0·501 ±0·082 mg g−1 min−1), 52 (0·410 ± 0·088 mg−1 g−1 min1) and 104 (0·397 ± 0·074 mg g−1 min−1) weeks.