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Keywords:

  • Male Topical Treatment;
  • Male Sex Steroid Replacement;
  • Male Design Methodology of Clinical Trials

ABSTRACT

Aim.  To compare the pharmacokinetics (PK), metabolism, intra- and inter-subject variability of a permeation-enhanced testosterone patch versus a topical testosterone gel.

Methods.  28 hypogonadal men were treated with a testosterone patch (5 mg/day applied at 2200 h) and a 1% testosterone gel (5 g/day applied at 0800 h; nominal delivery 5 mg/day), each for 14 days, in an open-label crossover design. PK profiles of total testosterone (TT) and calculated free testosterone (cFT) were measured on day 7 and day 14 of each treatment, with patches or gel applied to the abdomen; dihydrotestosterone (DHT) and estradiol (E2) profiles were measured on day 14. The time-average (Cavg), maximum (Cmax), time of maximum (Tmax) and minimum concentrations (Cmin) were derived from each profile. The intra- and inter-subject coefficients of variation (CVintra and CVinter) of the TT and cFT parameters were computed by ANOVA.

Results.  Nightly applications of the patch produced a mean TT profile that mimicked the circadian pattern of healthy men. Morning applications of the gel produced a flatter mean profile; though individual subjects exhibited significant peaks at variable times. For TT, the mean and 90% confidence intervals of the patch/gel ratio of Cavg (1.030; 0.936–1.133; P > 0.05) and Cmax (1.086; 0.974–1.211; P > 0.05) met the criteria for bioequivalence. Cmin was lower for the patch. DHT levels and DHT/T ratios were 2 to 3-fold higher for the gel (P < 0.0001). E2 levels and E2/T ratios were comparable. CVintra and CVinter for Tmax approached 100% for the gel and were 23% and 42%, respectively, for the patch (P < 0.0001). Other variability parameters were generally comparable. Both products were well tolerated, and the patches adhered well.

Conclusions.  These findings reflect the different mechanisms of transdermal absorption from the patch and gel and provide new considerations for selecting testosterone replacement therapies in hypogonadal men.