Lundborg P, Abrahamsson B, Wieselgren I, Walter M
Clinical Pharmacology, Clinical Research and Development, Astra Hässle AB, Mölndal, Sweden.
Eur J Clin Pharmacol. 1993;45(2):161-3. doi: 10.1007/BF00315499.
We have studied a controlled-release formulation containing metoprolol 100 mg and hydrochlorothiazide 12.5 mg. We compared the pharmacokinetics of both substances and the pharmacodynamics of metoprolol with those of a conventional combination tablet. The controlled-release formulation gave less variable plasma metoprolol concentrations, Cmax 138 nmol.l-1 and Cmin 74 nmol.l-1, whereas for the conventional formulation the mean Cmax of metoprolol was 629 nmol.l-1 and the Cmin 20 nmol.l-1. Despite lower relative systemic availability (68%) for metoprolol from the controlled-release formulation and a smaller AUC, metoprolol from the controlled-release formulation produced a greater total effect, calculated as the area under the curve of the effect on exercise heart rate vs. time (303 vs. 259%.h; P < 0.05). Hydrochlorothiazide was rapidly absorbed from both formulations and the plasma concentration profiles were almost superimposable. Controlled-release metoprolol with hydrochlorothiazide combines effective beta 1-adrenoceptor blockade for 24 h without affecting the pharmacokinetics of hydrochlorothiazide.
我们研究了一种含有100毫克美托洛尔和12.5毫克氢氯噻嗪的控释制剂。我们将这两种物质的药代动力学以及美托洛尔的药效动力学与传统复方片剂进行了比较。控释制剂使血浆美托洛尔浓度的变异性较小，Cmax为138纳摩尔/升，Cmin为74纳摩尔/升，而传统制剂中美托洛尔的平均Cmax为629纳摩尔/升，Cmin为20纳摩尔/升。尽管控释制剂中美托洛尔的相对全身可用性较低（68%）且AUC较小，但控释制剂中的美托洛尔产生了更大的总效应，以运动心率对时间的效应曲线下面积计算（303对259%·小时；P<0.05）。两种制剂中的氢氯噻嗪均迅速吸收，血浆浓度曲线几乎重叠。含氢氯噻嗪的控释美托洛尔可有效阻断β1肾上腺素能受体达24小时，且不影响氢氯噻嗪的药代动力学。
