Pharmacokinetic characteristics, efficacy, and safety of buccal testosterone in hypogonadal males: a pilot study.

Transbuccal administration of drugs provides an easy route of administration. To test the safety and efficacy of a novel testosterone (T) product, we performed a randomized, double blind, placebo-controlled study in a parallel design. Men with serum T levels below 250 ng/dL were administered either an active buccal tablet containing 10 mg T (n = 7) or a buccal placebo tablet (n = 6) containing 3 mg pseudoephedrine HCl for taste matching. Men were studied while taking a standard T enanthate dose, after 6 weeks of a wash-out period, and after 8 weeks of therapy. The men were matched for age (mean +/- SD, 41 +/- 16 vs. 47 +/- 16) and type of hypogonadism (three primary testicular failures in each group, with the remainder having a central etiology). Acute pharmacokinetic testing showed peak serum hormone levels at 30 min, with a mean serum T concentration of 2688 +/- 147 ng/dL (range, 1820-3770 ng/dL). Levels returned to baseline in 4-6 h, resulting in a total T area under the curve level of 3865 ng/hn.dL, less than that using other available forms of T administration. Similar pharmacokinetics were observed for the hormone's metabolites, bioavailable T, free T, and estradiol. After 8 weeks of treatment, the results of nocturnal penile tumescence studies evaluating rigidity and circumference were significantly different from those in the placebo group (P < 0.05) and comparable to those during T enanthate therapy. In conclusion, transbuccal T therapy was sufficient to maintain normal sexual function while minimizing the total time of exposure to elevated circulating serum T levels.