Rolf C, Gottschalk I, Behre H M, Rauch C, Thyroff U, Nieschlag E
Institute of Reproductive Medicine of the University Münster, Holzkirchen, Germany.
Exp Clin Endocrinol Diabetes. 1999;107(1):63-9. doi: 10.1055/s-0029-1212075.
In a phase I single-center, open, randomized pilot study with a three-way cross-over design the pharmacokinetics of three testosterone-containing transdermal therapeutic systems were evaluated in healthy male volunteers. Testosterone TTS HEXAL type 1 and 2 are nonscrotal membrane patches differing in the kind of adhesive used. 6 subjects were treated with low dose Testosterone TTS type 1, high dose Testosterone TTS type 1 and low dose Testosterone TTS type 2. To eliminate the influence of endogenous serum testosterone, the endogenous testosterone secretion was suppressed by the GnRH antagonist cetrorelix. In all subjects under GnRH antagonist treatment a marked suppression of LH, FSH, testosterone, DHT and estradiol was observed. Physiologic testosterone levels were achieved during the 24-hour-application period. Maximal serum levels were reached after 4 hours with both TTS systems. Both systems appear suited for further testing because both enable a physiological circadian profile to be achieved. GnRH-antagonist pretreatment is a useful model to evaluate the effect of exogenous testosterone in clinical studies, when, due to fluctuations in endogenous hormone levels, an estimation of the proportion of exogenous steroid is not possible.
在一项采用三向交叉设计的I期单中心、开放、随机试验研究中，对三种含睾酮的透皮治疗系统在健康男性志愿者中的药代动力学进行了评估。睾酮TTS HEXAL 1型和2型是非阴囊膜贴片，所用粘合剂类型不同。6名受试者分别接受低剂量睾酮TTS 1型、高剂量睾酮TTS 1型和低剂量睾酮TTS 2型治疗。为消除内源性血清睾酮的影响，采用GnRH拮抗剂西曲瑞克抑制内源性睾酮分泌。在所有接受GnRH拮抗剂治疗的受试者中，观察到LH、FSH、睾酮、双氢睾酮和雌二醇均受到显著抑制。在24小时用药期间达到了生理睾酮水平。两种TTS系统均在4小时后达到最大血清水平。两种系统似乎都适合进一步测试，因为它们都能实现生理昼夜节律。当由于内源性激素水平波动而无法估计外源性类固醇比例时，GnRH拮抗剂预处理是评估临床研究中外源性睾酮作用的有用模型。
