Zimmermann T, Seiberling M, Thomann P, Karabelnik D
G. Pohl-Boskamp GmbH & Co., Hohenlockstedt, Schweiz.
Arzneimittelforschung. 1995 Nov;45(11):1198-201.
An open, randomized cross-over trial was performed in 20 healthy volunteers to evaluate the relative bioavailability and the pharmacokinetics of myrtol standardized, the active ingredient of Gelomyrtol and Gelomyrtole forte capsules (abbreviated as GE and GF, respectively, in the following text). The male subjects, aged 19 to 42 years, were given in a randomized manner 1 capsule of GE (120 mg myrtol stand.) uncrushed, 1 capsule of GE crushed, 1 capsule of GF (300 mg myrtol stand.) uncrushed and 1 capsule of GF crushed on 4 different days. The time of administration was always about 8 a.m. and the medication had to be swallowed with 200 ml water. The 4 study sessions were separated (correction of spearated] by at [correction of a] least 6 days. Prior to and 15, 30, 45, 60, 75, 120, 150 min and 3, 4, 5, 8, 12 and 24 h after medication at least 10 ml blood were taken from an antecubital vein. The blood samples were centrifuged within 20 min, the plasma was separated, and transferred into tubes and immediately deep-frozen at -20 degrees centigrade. From GE capsules cineol as main component was absorbed to 93,2% and from GF capsules to 95,6% based on the comparison of the uncrushed with the crushed capsules. The geometric mean of Cmax was 72,4 ng/ml for GE uncrushed capsules, a value of 33% below that for the crushed ones. The time to peak (tmax) was three times higher. With GF Cmax reached 238,2 ng/ml for the uncrushed capsules, a value of 36% below the one for the crushed ones and tmax was 67% higher. The time until the appearance of measurable plasma concentrations (tlag) was 7 and 5 times higher, respectively. These results show, that the main components of myrtol standardized, the active ingredient of GE and GF, are absorbed about 100% compared to the liquid form of administration (crushed capsule). The enteric coating of the capsules produces lower plasma peak-concentrations at later time points. This results in a plateau-like phase of the concentration/time curve between the 2nd and the 8th hour after application and reveals a considerable therapeutic advantage of the enteric coating.
在20名健康志愿者中进行了一项开放、随机交叉试验，以评估标准桃金娘油（Gelomyrtol和Gelomyrtole forte胶囊的活性成分，以下文本中分别简称为GE和GF）的相对生物利用度和药代动力学。19至42岁的男性受试者在4个不同日期随机服用1粒未碾碎的GE胶囊（120mg标准桃金娘油）、1粒碾碎的GE胶囊、1粒未碾碎的GF胶囊（300mg标准桃金娘油）和1粒碾碎的GF胶囊。给药时间总是在上午8点左右，药物必须用200ml水吞服。4个研究阶段至少间隔6天。在给药前以及给药后15、30、45、60、75、120、150分钟和3、4、5、8、12和24小时，从前臂静脉采集至少10ml血液。血样在20分钟内离心，分离出血浆，转移至试管中，并立即在-20摄氏度下深度冷冻。根据未碾碎胶囊与碾碎胶囊的比较，GE胶囊中作为主要成分的桉叶油醇吸收了93.2%，GF胶囊中吸收了95.6%。未碾碎的GE胶囊的Cmax几何平均值为72.4ng/ml，比碾碎的胶囊低33%。达峰时间（tmax）高出三倍。对于GF胶囊，未碾碎的胶囊Cmax达到238.2ng/ml，比碾碎的胶囊低36%，tmax高出67%。出现可测量血浆浓度的时间（tlag）分别高出7倍和5倍。这些结果表明，与液体给药形式（碾碎的胶囊）相比，GE和GF的活性成分标准桃金娘油的主要成分吸收约100%。胶囊的肠溶包衣在较晚时间点产生较低的血浆峰值浓度。这导致给药后第2至8小时浓度/时间曲线出现类似平台期，并显示出肠溶包衣具有显著的治疗优势。
