Bai S A, Walle U K, Walle T
J Pharmacokinet Biopharm. 1985 Jun;13(3):229-41. doi: 10.1007/BF01065654.
The intravenous and oral dose kinetics of propranolol were studied in the dog both in a fasted state and immediately after a meal consisting of 100 g of cooked beef liver. Fifty microCi of 3H-propranolol was administered intravenously simultaneously with a 40-mg oral dose of unlabeled propranolol. Plasma 3H-propranolol was measured by specific extraction and liquid scintillation spectrometry, and unlabeled plasma propranolol was determined by gas chromatography-mass spectrometry. Feeding significantly reduced (25%) the elimination half-life and increased (52%) the systemic clearance of intravenous propranolol. The increase in the systemic clearance of propranolol after feeding was mostly due to an increase (60%) in apparent hepatic blood flow, which appeared to remain elevated for 5-7 hr. The meal had no influence on the apparent volume of distribution or plasma binding. Feeding did not affect the area under the concentration-time curve of oral propranolol, but significantly delayed the rate of oral propranolol absorption, shifting the time to reach peak plasma levels from 60 to 158 min. The results of this study suggest that feeding alters the disposition of propranolol in the dog by producing a sustained increase in hepatic blood flow.
在禁食状态下以及在食用100克熟牛肝后，对犬体内普萘洛尔的静脉和口服剂量动力学进行了研究。静脉注射50微居里的³H - 普萘洛尔的同时口服40毫克未标记的普萘洛尔。通过特定萃取和液体闪烁光谱法测量血浆³H - 普萘洛尔，通过气相色谱 - 质谱法测定未标记的血浆普萘洛尔。进食显著缩短了静脉注射普萘洛尔的消除半衰期（25%）并增加了其全身清除率（52%）。进食后普萘洛尔全身清除率的增加主要是由于表观肝血流量增加（60%），且该增加似乎持续5 - 7小时。进食对表观分布容积或血浆结合无影响。进食不影响口服普萘洛尔的浓度 - 时间曲线下面积，但显著延迟了口服普萘洛尔的吸收速率，使达到血浆峰值水平的时间从60分钟延长至158分钟。本研究结果表明，进食通过使肝血流量持续增加来改变犬体内普萘洛尔的处置。
