Comparison of the steady-state pharmacokinetics, metabolism, and variability of a transdermal testosterone patch versus a transdermal testosterone gel in hypogonadal men.

Author(s): Mazer N, Bell D, Wu J, Fischer J, Cosgrove M, Eilers B, BS, RN,

Affiliation(s): Watson Laboratories, Inc., Medical Affairs, Salt Lake City, UT 84124, USA. t42nam@comcast.net

Publication date & source: 2005-03, J Sex Med., 2(2):213-26.

Publication type: Randomized Controlled Trial

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.