Topical Steroidal Formulations

Temple University
posted on 03/05/2009

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The inventors and other investigators have found that that the adrenal steroid DHEA inhibits the development of several types of experimental cancers and atherosclerosis in various animal models. The steroid also reduces weight gain in obese animals and produces a striking anti-diabetic effect. There are compelling data that DHEA exerts its actions primarily through two biological mechanisms: 1)inhibition of glucose-6-phosphate dehydrogenase(G6PD) with a consequent reduction in NADPH-dependent oxygen-free radical production, which likely contributes to the anti-carcinogenic and anti-atherosclerotic effects of the steroid, and 2)antagonizing the action of cortisol(anti-glucorticoid effect). There is increasing evidence that excess cortisol production plays an important role in the development of the metabolic syndrome, and we have evidence that the anti-glucorticoid effect of DHEA is primarily responsible for its anti-obesity and anti-diabetic actions in laboratory animals.

DHEA can be metabolized into androgenic (testosterone) and estrogenic (estrone and estradiol) hormones, and this greatly limits its potential use as a drug. We have developed the synthetic steroid, fluasterone, which in animal studies lacks the androgenic and estrogenic side-effects of DHEA and is a more potent inhibitor of G6PD and cortisol action. In animal tests fluasterone is about 6-times as active as DHEA as an anti-glucorticoid and is a potent anti- diabetic. In early clinical trials, an oral formulation of fluasterone lowered fasting plasma triglycerides in patients with the metabolic syndrome.
We have found that the DHEA steroids (including fluasterone) undergo rapid metabolism in the liver and/or gastrointestinal tract when given orally, necessitating the use of very high oral dosages to achieve efficacy. Thus, oral administration is not a practical means of drug delivery. We have recently developed a transdermal formulation of fluasterone, which in animal models is 40-times to 80-times as potent as oral administration.

Diabetes, Obesity

• Lacks the sex-hormonal side-effects of DHEA
• Is a potent anti-diabetic in preclinical studies and works through a mechanism distinct from existing anti-diabetic drugs. Unlike most anti- diabetic drugs on the market it does not cause undesirable weight gain, and may actually reduce weight
• Can be administered transdermally in a topical gel