Svensson C K, Mauriello P M, Barde S H, Middleton E, Lalka D
Clin Pharmacol Ther. 1984 May;35(5):660-5. doi: 10.1038/clpt.1984.91.
Recent experiments suggest that propranolol taken orally with a carbohydrate-rich meal increases its apparent bioavailability by reducing first-pass metabolism. It has been postulated that this increase in bioavailability may be secondary to a transient increase in hepatic blood flow (QH). To examine this hypothesis, we examined the effect of one of the carbohydrate meals (potato) tested in other propranolol studies on QH by measuring blood clearance (ClB) of indocyanine green (ICG). Ten minutes after eating 200 gm cooked potato, mean ICG blood clearance (ClB) in six subjects rose by 12% (range -13% to +41%). There also was a 10% mean increase (range -13% to +23%) in ICG ClB 60 min after the meal. It was then postulated that a larger carbohydrate meal might induce a more consistent and substantial increase in ICG ClB; therefore, five of the subjects were restudied after 400 gm potato. The increase in ICG ClB was of the order of that after 200 gm. Changes in QH of this magnitude would be expected to make a negligible contribution to the mean 50% increase in propranolol bioavailability reported by several investigators. It thus appears that factors other than change in QH play a dominant role in the reduced first-pass metabolism of propranolol after a meal rich in carbohydrates.
近期实验表明，普萘洛尔与富含碳水化合物的餐食一起口服时，可通过减少首过代谢来提高其表观生物利用度。据推测，生物利用度的这种增加可能继发于肝血流量（QH）的短暂增加。为了验证这一假设，我们通过测量吲哚菁绿（ICG）的血液清除率（ClB），研究了在其他普萘洛尔研究中测试的一种碳水化合物餐食（土豆）对QH的影响。食用200克煮熟的土豆10分钟后，6名受试者的平均ICG血液清除率（ClB）升高了12%（范围为-13%至+41%）。餐后60分钟，ICG ClB平均也升高了10%（范围为-13%至+23%）。随后推测，更大剂量的碳水化合物餐食可能会使ICG ClB产生更一致且显著的升高；因此，对其中5名受试者在食用400克土豆后再次进行了研究。ICG ClB的升高幅度与食用200克土豆后相当。这种程度的QH变化预计对几位研究者报告的普萘洛尔生物利用度平均升高50%的贡献可忽略不计。因此，似乎除了QH变化之外，其他因素在富含碳水化合物餐后普萘洛尔首过代谢降低中起主导作用。
