ORAL ANDROGENS IN MAN-3: PK OF ORAL TESTOSTERONE BY ALPHA5-DUTASTERIDE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: This study was designed to evaluate the efficacy of oral delivery of testosterone (T) when co-administered with dutasteride (D), comparing nanomilled T (NmT+D) versus T dissolved in Capmul (CpT+D). Methods: Twelve normal men were administered leuprolide on Day -14 to suppress endogenous T biosynthesis. Subjects also received a single loading dose of D (24.5mg) on Day -14 followed by daily doses (0.5 mg) for 24 days. For T treatment, subjects were administered CpT+D, 200 mg on day 1 (fasted), 400 mg on day 2 (fasted), and 400 mg on day 3 (fed). The following week this regimen was repeated using NmT+D. Serum T and dihydrotestosterone (DHT) were measured: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours after each dose. Results: Two weeks after leuprolide administration T levels were below the normal range. Mean serum T was increased above the lower limit of the normal range for 8-10 hours with 400 mg of both formulations of oral T+D. In the fasting state, CpT+D exhibited a greater AUC0-24 and Cmax than NmT+D. Food had minimal effect on the PK of either formulation. Serum DHT remained below the normal range throughout the study period with both formulations. No significant changes in liver function tests or other adverse events were observed. Conclusions: A 400 mg dose of either oral formulation normalized serum T for 8-10 hours and suppressed DHT, demonstrating the feasibility of oral T as promising therapy for the treatment of male hypogonadism.