Iwamoto K, Watanabe J, Yonekawa H
Department of Pharmacy, Shimane Medical University Hospital, Izumo, Japan.
J Pharm Pharmacol. 1989 Jun;41(6):398-401. doi: 10.1111/j.2042-7158.1989.tb06485.x.
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 micrograms mL-1) prepared in oxygenated, pH 7.4 Krebs-Ringer bicarbonate buffer solution (20 mL) containing 3% BSA for 60 min at 37 degrees 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 micrograms 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 micrograms mL-1), 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 min-1) and 104 (0.397 +/- 0.074 mg g-1 min-1) weeks.
为研究年龄对普萘洛尔肺摄取的影响，将从3至104周龄大鼠分离的肺组织切碎（0.4 g），与在含3%牛血清白蛋白的充氧pH 7.4 Krebs-Ringer碳酸氢盐缓冲溶液（20 mL）中配制的药物（1至500微克/毫升）在37℃孵育60分钟。在当前体外条件下，任何年龄组中普萘洛尔的代谢均不显著（即小于任何初始负荷的0.6%）。用2.5微克/毫升药物孵育后，摄取程度在7周龄时最大（即初始负荷的82%），在3周龄（64%）、24周龄（61%）、52周龄（51%）和104周龄（48%）大鼠中相对较小。在药物的组织与培养基浓度比中也观察到类似的特定年龄依赖性。在任何年龄组中，孵育前5分钟获得的初始摄取率是明显的线性转运和可饱和（容量限制）过程的组合。容量限制摄取率存在明显的特定年龄依赖性。尽管Km'值在任何年龄组中几乎相当（即24.4至25.4微克/毫升），但Vmax表现出特定年龄依赖性，在7周龄时最高（0.726±0.101毫克/克/分钟），在3周龄（0.501±0.082毫克/克/分钟）、52周龄（0.410±0.088毫克/克/分钟）和104周龄（0.397±0.074毫克/克/分钟）时相对较低。
