目的 研究口服给予不同配比比索洛尔 / 氢氯噻嗪的复方制剂在健康志愿者中的药动学。 方法 采用双盲、单次给药试验方法,入选受试者均分成 3 组,每组受试者接受比索洛尔 / 氢氯噻嗪 3 种配比( 2.5 mg/6.25 mg , 5.0 mg/6.25 mg , 10 mg/6.25 mg )中的一种。用反相高效液相法分别测定血浆中比索洛尔和氢氯噻嗪的浓度和尿样中的浓度,计算主要药动学参数。 结果 比索洛尔 / 氢氯噻嗪中比索洛尔在 3 种配比 (2.5 mg/6.25 mg , 5.0 mg/6.25 mg , 10 mg/6.25 mg) 中的 <> ρ max 分别为 (9.4±1.9) , (20.7±2.5) , (32.6±4.1)μg·L-1 ;达峰时间分别为 (2.7±0.5) , (2.3±1.5) , (2.7±1.5)h ; <> t 1/2 分别为 (10.3±2.1) , (10.9±2.3) , (9.8±2.1)h ;药时 AUC0-36 分别为 (143.2±33.5) , (303.8±41.91) , (459.7±93.0)μg·h·L-1 ; 36 h 尿药回收率分别为 41.8±9.4% , 38.3±7.5% , (37.6±11.6)% 。比索洛尔 / 氢氯噻嗪中氢氯噻嗪在 3 种配比中的 <> ρ max 分别为 (41.7±7.8) , (36.5±6.8) , (36.1±7.8)μg·L-1 ;达峰时间分别为 (2.8±1.0) , (2.5±0.6) , (2.8±0.4)h ;药时 AUC0-24 分别为 (265.8±58.9) , (252.0±47.2) , (237.9±43.5) μg·h·L-1 ; <> t 1/2 分别为 (10.6±2.3) , (9.1±1.7) , (9.7±1.5)h ; 36 h 尿药回收率分别为 (56.3±16.2)% , (55.0±9.9)% , (49.3±17.3)% 。 结论 在 3 种配比中,比索洛尔呈现线性药动学特征,氢氯噻嗪的药动参数在 3 种配比中保持不变。
Abstract
OBJECTIVE To investigate the pharmacokinetic characteristics of bisoprolol and hydrochlorothiazide with different combinations in healthy volunteers. METHODS A double-blind, single-dose, randomized clinical trial was conducted. 30 volunteers were orally administered with bisoprolol/hydrochlorothiazide combination tablets with the contents of 2.5 mg/6.25 mg, 5.0 mg/6.25 mg, 10 mg/6.25 mg. The concentrations of bisoprolol and hydrochlorothiazide in plasma and urine were determined by high-performance liquid chromatographic methods. The pharmacokinetic parameters were calculated. RESULTS Main pharmacokinetic parameters of bisoprolol in three combinations were as follows: ρmax (9.4±1.9), (20.7±2.5) and (32.6±4.1) μg·L-1; tmax (2.7±0.5),(2.3±1.5) and (2.7±1.5)h;t1/2 (10.3±2.1),(10.9±2.3) and (9.8±2.1)h; AUC0-36 (143.2±33.5),(303.8±41.91) and (459.7±93.0)μg·h·L-1, respectively. The urinary recoveries of bisoprolol within 36 h after a single dose were (41.8±9.4)%,(38.3±7.5)% and (37.6±11.6)%,respectively. The main pharmacokinetic parameters of hydrochlorothiazide in three combinations were as follows: ρmax (41.7±7.8),(36.5±6.8) and (36.1±7.8)μg·L-1;tmax (2.8±1.0),(2.5±0.6) and (2.8±0.4)h; AUC0-24 (265.8±58.9),(252.0±47.2) and (237.9±43.5) μg·h·L-1; t1/2 was (10.6±2.3),(9.1±1.7) and (9.7±1.5) h, respectively. The urinary recoveries of hydrochlorothiazide within 36 h after single dose were (56.3±16.2)%,(55.0±9.9)% and (49.3±17.3)%,respectively. CONCLUSION Three combinations of bisoprolol showed linear pharmacokinetic properties, while the pharmacokinetic parameters of hydrochlorothiazide were unchanged.
关键词
比索洛尔 /
氢氯噻嗪 /
药动学 /
高效液相色谱法
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Key words
bisoprolol /
hydrochlorothiazide /
pharmacokinetics /
HPLC
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参考文献
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( 收稿日期 : 2009-02-08 )
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