AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2011;3(3):275-283

Original Article
Phase I and Phase II clinical trials of androst-5-ene-3β,7β,17β-triol

Dwight R. Stickney, Clarence N. Ahlem, Elizabeth Morgan, Christopher L. Reading, Nanette Onizuka, James M.

Harbor Biosciences, Inc., 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USA.

Received February 14, 2011; Accepted March 28, 2011; Epub April, 2011; Published April 15, 2011

Abstract: The immune regulating DHEA metabolite, androst-5-ene-3β,7β,17β-triol (βAET), was evaluated for
safety, cholesterol lowering, and vaccine enhancement in phase I and phase II clinical trials.  Safety and
pharmacokinetics were evaluated in one study of normal subjects that received βAET or placebo transmucosally
(buccal tablets) for 4 days.  In a second study βAET was given by daily subcutaneous injection for 3 days.  βAET
was subsequently evaluated in placebo-controlled trials for cholesterol lowering in hyperlipidemic subjects and
for vaccine potentiation of hepatitis B surface antigen (HBsAg) in elderly subjects.  Adverse events were primarily
associated with injection site reactions.  Pharmacokinetics indicated that βAET was rapidly cleared after either
route of administration in both normal and elderly subjects.  Plasma βAET concentrations typically declined below
the limit of detection within a few hours of administration.  βAET pharmacokinetics was similar in males and
females and in normal and elderly subjects.  βAET significantly lowered cholesterol in normal adult, but not in
elderly or hyperlipidemic subjects.  HBsAg titers were not increased in elderly βAET treated subjects relative to
placebo. Conclusions: Short-term administration of βAET is safe in humans.  βAET has a cholesterol lowering
effect in healthy humans, but not hyperlipidemics.  Exogenous βAET appeared to be rapidly metabolized, which
may be consequential to the lack of pharmacological activity.  A longer duration of treatment with higher doses or
chemical derivatives that are resistant to metabolic inactivation are likely necessary to treat human disease.  The
utility of βAET in humans may be limited to maintenance of homeostasis in healthy adults. (AJTR1103004).

Keywords: Androstenetriol, safety, pharmacokinetics, βAET

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Address all correspondence to:
Clarence N. Ahlem, PhD
Harbor Biosciences, Inc.
9171 Towne Centre Drive
Suite 180, San Diego
CA 92122, USA.