McAinsh J, Holmes B H, Fitzsimons T J, Young J
Biopharm Drug Dispos. 1986 May-Jun;7(3):223-31. doi: 10.1002/bdd.2510070303.
In this comparative bioavailability study in 12 healthy volunteers the blood level profiles and urinary recoveries of both atenolol and chlorthalidone were studied following the administration of the drugs as a fixed combination ('Tenoret 50'), as a free combination, and individually, at doses of 50 mg atenolol and 12.5 mg chlorthalidone. There were no statistically or clinically significant differences between the three treatments of atenolol in terms of individual blood levels, areas under the curve, and urinary excretion. The mean half-lives were between 5 and 7 h, in agreement with other published data. The variation in peak systemic levels is less than that observed for a number of other beta-blocking drugs and is of the same order as seen in other investigations involving atenolol. Thus the bioavailability of atenolol from the fixed combination is equivalent to that from the free combination and from the atenolol tablet. The mean peak blood concentrations of chlorthalidone were 0.94, 1.00, and 0.99 micrograms ml-1 for the fixed and free combinations and the chlorthalidone tablet, respectively. The mean areas under the curve were also similar as were the mean half-lives and urinary recovery. There were no statistically or clinically significant differences between the three treatments. Thus the bioavailability of chlorthalidone from the fixed combination is equivalent to that from the free combination and from the chlorthalidone tablet. It is concluded that combining chlorthalidone and atenolol in a single tablet does not affect 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，研究了阿替洛尔和氯噻酮以固定组合（“复方阿替洛尔50”）、自由组合以及单独给药（剂量为50 mg阿替洛尔和12.5 mg氯噻酮）后的血药浓度曲线和尿回收率。在个体血药浓度、曲线下面积和尿排泄方面，阿替洛尔的三种治疗方法之间在统计学或临床上均无显著差异。平均半衰期在5至7小时之间，与其他已发表的数据一致。峰系统水平的变化小于许多其他β受体阻滞剂所观察到的变化，且与其他涉及阿替洛尔的研究中所见的变化程度相同。因此，固定组合中阿替洛尔的生物利用度与自由组合及阿替洛尔片剂的生物利用度相当。氯噻酮在固定组合、自由组合和氯噻酮片剂中的平均峰血药浓度分别为0.94、1.00和0.99 μg/ml-1。曲线下平均面积、平均半衰期和尿回收率也相似。三种治疗方法之间在统计学或临床上均无显著差异。因此，固定组合中氯噻酮的生物利用度与自由组合及氯噻酮片剂的生物利用度相当。结论是，将氯噻酮和阿替洛尔制成单片制剂不会影响任何一种成分的全身生物利用度。
