Effects of skin washing on systemic absorption of testosterone in hypogonadal males after administration of 1.62% testosterone gel

摘要

Objective: The impact of washing on the pharmacokinetics, systemic absorption and residual testosterone on the skin after application of a 1.62% testosterone gel was investigated in an open-label, randomized, three-way crossover study in hypogonadal men. Research design and methods: Twenty-four hypogonadal men (total testosterone 300ng/dL) applied 5g of 1.62% gel (81mg testosterone) once daily to the shoulders/upper arms for 7 days during each of three consecutive treatment periods. On the 7th dosing day of each period, the skin was washed (soap/water) at one of the following times: 2, 6, or 10 hours post-dose. Pharmacokinetic serum samples were collected at baseline, and on days 6 (no washing) and 7 (with washing) of each treatment period. Skin stripping for determination of residual testosterone was also performed on days 6 and 7. A single location on the application site was stripped a total of 10 times. Testosterone was extracted from the tape strips using ethanol, and concentrations were determined using high performance liquid chromatography with diode array detection (HPLC-UV). Main outcome measures: Testosterone C max, AUC 0-24, average concentration over the dosing interval (C av), and safety were assessed. Results: Washing at 2 and 6 hours caused a 10-14% decrease in AUC 0-24 and C av, but not C max. Washing 10 hours after gel application had no effect on C max, AUC 0-24, or C av. Skin washing decreased the mean amount of testosterone remaining on the skin surface by at least 81%. Conclusions: Washing the site of gel application as soon as 2 hours after application had little impact on bioavailability and was effective in reducing residual testosterone on the skin. This finding may be important to prevent secondary transfer. Study limitations: The experimental conditions using uniform timing and procedures for dose administration and washing may not fully reflect real world circumstances. Clinical Trial Registration NCT Numbers: Study was not registered (first subject enrolled 22 December 2006)