Transdermal testosterone gel: pharmacokinetics, efficacy of dosing and application site in hypogonadal men

OBJECTIVE To determine the regimen that would most effectively maintain serum testosterone concentrations in treated hypogonadal men within the normal reference range of 3-11.4 mug/L. PATIENTS AND METHODS Eighteen men aged 24-69 years with either primary or secondary hypogonadism participated in and 16 completed a randomized, six-treatment regimen, three-period (phase), three-way matrix-type crossover study. A 1% and 2% testosterone gel (CP601, Cellegy Pharmaceuticals, Inc., San Francisco, USA) was administered either once or twice daily transdermally at different body sites to determine optimal dosing, application sites, and its pharmacokinetics and tolerability in hypogonadal men. Treatments A-F included 1 g of 1% and 2% gel that was equivalent to 10 or 20 mg of testosterone, applied once or twice daily to the skin of either the thigh or the upper arm. Six men also participated in a study of 3 g of 2% gel that was equivalent to 60 mg of testosterone applied once daily, half on each thigh. Pharmacokinetic variables were calculated for testosterone for each man in each treatment period and the results analysed by ANOVA. RESULTS In general the higher dose regimens produced higher serum concentrations of testosterone; the 3 g/2% dose was most successful in maintaining serum testosterone within the normal reference range. The average testosterone concentration (C-avg) was 6.52 mug/L and all men had a C-avg of > 3.0 mug/L. The prediction of all men achieving a C-avg of > 3.0 mug/L was 96%. The mean minimum concentration (C-min) was 3.83 mug/L and half the patients had a C-min of > 3.0 mug/L. Most men had serum testosterone levels within the normal reference range throughout the 24 h, and the treatment was well tolerated. CONCLUSIONS The 3 g/2% dose applied to the skin daily resulted in serum testosterone in the normal reference range in most hypogonadal men. Dose adjustments to either a lower or higher dose should shift serum testosterone concentration to the desired range in those who do not achieve this range with this dose.