Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men

Summary

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 endogenousserum 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.

Key words

Testosterone - GnRH-antagonist - transdermal - pharmacokinetic