Journal of Andrology
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Published-Ahead-of-Print April 8, 2010, DOI:10.2164/jandrol.109.009746

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Pharmacokinetics of Two Novel Formulations of Modified Release Oral Testosterone Alone and with Finasteride in Normal Men with Experimental Hypogonadism

Christin N Snyder , Richard V Clark , Ralph B Caricofe , Mark A Bush , Mara Y Roth , Stephanie T Page , William J Bremner , and John K Amory *

* To whom correspondence should be addressed. E-mail: jamory{at}u.washington.edu.

Oral administration of testosterone might be useful for the treatment of testosterone deficiency. However, current "immediate-release" formulations of oral testosterone exhibit suboptimal pharmacokinetics, with supraphysiological peaks of testosterone and its metabolite, dihydrotestosterone (DHT), immediately after dosing. To dampen these peaks, we have developed two novel modified release formulations of oral testosterone designed to slow absorption from the gut and improve hormone delivery. We studied these testosterone formulations in sixteen normal young men enrolled in a two-arm, open-label clinical trial. Three hundred and six hundred milligram doses of immediate-release, and modified fast-release or slow-release formulations were administered sequentially to eight normal men rendered hypogonadal by the administration of the gonadotropin releasing hormone (GnRH) antagonist acyline. Blood for measurement of serum testosterone, DHT, and estradiol was obtained before and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after each dose. A second group of eight men was studied with the co-administration of 1 mg of the 5alpha-reductase inhibitor, finasteride, daily throughout the treatment period. Serum testosterone was increased with all formulations of oral testosterone. The modified slow-release formulation significantly delayed the post-dose peaks of serum testosterone and reduced peak concentrations of serum DHT compared to the immediate-release formulation. The addition of finasteride further increased serum testosterone and decreased serum DHT. We conclude that the oral modified slow-release testosterone formulation exhibits superior pharmacokinetics compared to immediate-release oral testosterone both alone and in combination with finasteride. This formulation might have efficacy for the treatment of testosterone deficiency.


Key words: Androgen • 5-alpha-reductase • dihydrotestosterone • drug delivery • estradiol






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