TESTOSTERONE PHARMACOKINETICS AFTER APPLICATION OF AN INVESTIGATIONALTRANSDERMAL SYSTEM IN HYPOGONADAL MEN

This open-label, randomized, placebo lead-in, three-treatment crossove r study in 19 hypogonadal men (27-82 years of age) evaluated dose prop ortionality of serum testosterone concentrations with application of o ne or two investigational transdermal testosterone systems for applica tion to the arm or torso. Testosterone in vivo kinetics profiles were determined using DeMonS, a recently developed numerical deconvolution method that estimates drug absorption at different time intervals and/ or drug disposition model parameters. After application of the investi gational transdermal systems, the mean serum testosterone, dihydrotest osterone, estradiol, and free testosterone concentrations were elevate d to normal levels. Treatment allowed approximation of the normal circ adian pattern of endogenous testosterone secretion, and the increase i n serum testosterone concentrations was proportional to the surface ar ea of systems applied. The investigational transdermal system provided effective testosterone replacement therapy as judged by pharmacokinet ic parameters.