Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers

Objectives: To evaluate the safety and pharmacokinetics of 3-acetyl-7-oxo-D HEA (3 beta -acetoxyandrost-5-ene-7.17-dione) given orally. Design: A randomized, double blind, placebo-controlled, escalating dose stu dy. Setting: The Chicago Center for Clinical Research. Participants: Twenty-two healthy men. Study method: The participants received placebo (n = 6) or 3-acetyl-7-oxo-D HEA (n = 16) at 50 mg/d for 7 days followed by a 7-day washout; 100 mg/d fo r 7 days followed by a 7-day washout; and 200 mg/d for 28 days. Outcome measures: Safety parameters, evaluated at each dose level, included measurement of total testosterone, free testosterone, dihydrotestosterone, estradiol, cortisol, thyroxin and insulin levels. Analyses for 7-oxo-DHEA- 3 beta -sulfate (DHEA-S), the only detectable metabolic product of the admi nistered steroid, were conducted on plasma drawn from all subjects at 0.25, 0.5, 1, 2, 4, 6 and 12 hours after the final 100 mg dose of 3 beta -acetyl -7-oxo-DHEA IEA. Results: There were no differences in the clinical laboratory values or in reported minor adverse experiences, between treatment and placebo groups. I n general, blood hormone concentrations were unaffected by the treatment wi th 3 beta -acetyl-7-oxo-DHEA and remained within the normal range. No chang es in vital signs, blood chemistry or urinalysis occurred during treatment with 3 beta -acetyl-7-oxo-DHEA compared to placebo. The administered steroi d was not detected in the blood but was rapidly converted to 7-oxo-DHEA-S, the concentrations of which were proportional to dose. This steroid sulfate did not accumulate; plasma concentrations 12 hours after the 3 beta -acety l-7-oxo-DHEA dose at 7 and 28 days on the 200 mg/d dose were 15.8 and 16.3 mug/L respectively. The mean time to peak plasma level of 7-oxo-DHEA-S was 2.2 hours; the mean half life was 2.17 hours. The apparent clearance averag ed 172 L/h, and the apparent mean volume of distribution was 540 L. Conclusion: These results indicate that 3 beta -acetyl-7-oxo-DHEA is safe a nd well tolerated in normal healthy men at doses up to 200 mg/d for 9 weeks .