McAinsh J, Holmes B F, Baber N S, Young J
Biopharm Drug Dispos. 1981 Apr-Jun;2(2):167-75. doi: 10.1002/bdd.2510020209.
In this comparative bioavailability study in 12 healthy volunteers the blood level profiles of both propranolol and bendrofluazide were studied following the multiple oral administration of the drugs as a fixed combination (Inderetic) and as a free combination at doses of 80 mg propranolol twice daily and 2.5 mg bendrofluazide twice daily. There were no statistically significant differences between the two regimens in terms of individual propranolol blood levels, half-lives and areas under the curve. The half-lives were between 5 and 8 h. Thus the bioavailability of propranolol from the fixed combination is equivalent to that from the free combination. The mean peak bendrofluazide blood levels were slightly higher following the administration of the fixed combination. This difference was statistically significant only at 1 and 2 h after the first dose. There were no statistically significant differences between these two bendrofluazide regimens in terms of half-life and area under the curve. Thus the bioavailability of bendrofluazide from the fixed combination is equivalent to that from the free combination. It is concluded therefore that by combining bendrofluazide and propranolol in a fixed capsule formulation does not affect significantly the systemic bioavailability of either component.
在这项针对12名健康志愿者的比较生物利用度研究中，研究了普萘洛尔和苄氟噻嗪在以固定组合（复方制剂）和自由组合形式多次口服给药后的血药浓度曲线，给药剂量为每日两次，每次80mg普萘洛尔和每日两次，每次2.5mg苄氟噻嗪。两种给药方案在个体普萘洛尔血药浓度、半衰期和曲线下面积方面无统计学显著差异。半衰期在5至8小时之间。因此，固定组合中普萘洛尔的生物利用度与自由组合中的相当。服用固定组合后，苄氟噻嗪的平均血药峰浓度略高。仅在首剂给药后1小时和2小时，这种差异具有统计学显著性。这两种苄氟噻嗪给药方案在半衰期和曲线下面积方面无统计学显著差异。因此，固定组合中苄氟噻嗪的生物利用度与自由组合中的相当。因此得出结论，将苄氟噻嗪和普萘洛尔制成固定胶囊制剂不会显著影响任何一种成分的全身生物利用度。
