Iwamoto K, Watanabe J, Yonekawa H
Department of Hospital Pharmacy, Shimane Medical University, Izumo, Japan.
J Pharm Pharmacol. 1988 Jun;40(6):445-7. doi: 10.1111/j.2042-7158.1988.tb06315.x.
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.
从7周龄大鼠分离出的肺脏，用含有1至100微克/毫升普萘洛尔和3%牛血清白蛋白的pH 7.4 Krebs-Ringer碳酸氢盐缓冲溶液（35毫升）以8毫升/分钟的再循环速率进行灌注。在初始负荷低于10微克/毫升时，获得了几乎平行的双指数药物浓度-时间曲线，而在100微克/毫升灌注后发现相对缓慢的单指数下降。当以1至10微克/毫升加载时，对灌注液普萘洛尔浓度-时间曲线进行药代动力学分析，得到的肺灌注清除率值几乎相当（0.387±0.092至0.486±0.095毫升/分钟/克）。相比之下，在100微克/毫升时该参数显著降低（0.113±0.042毫升/分钟/克）。目前的研究结果表明，普萘洛尔体外肺清除存在饱和动力学趋势。
