Pharmacokinetics, bioefficacy, and safety of sublingual testosterone cyclodextrin in hypogonadal men: comparison to testosterone enanthate--a clinical research center study.

Abstract

We studied and compared the pharmacokinetics and bioefficacy of two doses of sublingual testosterone cyclodextrin (SLT; 2.5 and 5.0 mg, administered three times per day) with testosterone enanthate (TE; 200 mg) given once every 20 days by im injections over a 60-day study period in 63 hypogonadal men. After SLT administration, serum testosterone (T) levels peaked at 20 min and then fell, reaching baseline levels by 360 min. The calculated half-lives were 60.3 +/- 7.5 and 68.8 +/- 5.0 min after a single dose of 2.5 and 5.0 mg SLT, respectively. The mean area under curve (AUC) of serum T was computed over 20-day periods for the 3 treatment groups. The mean net AUC of serum T after TE administration was about 4- and 2-fold higher than that in the 2.5 and 5 mg groups over the last 20 days. Serum estradiol and dihydrotestosterone followed the same pattern as serum T. Serum estradiol to T ratios decreased after T replacement in all 3 groups, whereas serum dihydrotestosterone to T ratios were not significantly changed by T treatment. Suppression of serum LH and FSH levels was more marked in the patients treated with TE than in those given SLT. Similarly, serum sex hormone-binding globulin levels showed significant decreases with androgen replacement only in the TE and SLT 5.0 mg range groups. There were no significant adverse effects based on comprehensive physical examinations, urea, electrolytes, and renal or liver function tests. Hematocrit levels increased in the TE-treated group, but remained slightly lower than baseline levels in the SLT groups. Serum high density lipoprotein cholesterol showed a small, but significant, decrease with time of treatment in all groups. Despite the differences in the AUC of serum T levels achieved by different androgen replacement therapies, all patients showed significant improvements in sexual motivation and performance, with no significant difference between the treatment groups. We conclude that SLT may be a useful addition to the currently available injectable and transdermal delivery systems for treatment of hypogonadal men. Because of the ease of administration, rapid reversibility of effects, and lower AUC of serum T levels achieved compared to those of TE injections, SLT may be especially suitable for treatment of boys with delayed puberty and older men with androgen deficiency.

Acute resistance exercise does not change the hormonal response to sublingual androstenediol intake

“…In contrast, sublingual testosterone intake causes peak serum testosterone concentrations to be reached »20-30 min after intake (Stuenkel et al 1991;Salehian et al 1995). In the present study SL-DIOL intake caused increased serum testosterone concentrations for at least 180 but not 240 min.…”

“…In the present study SL-DIOL intake caused increased serum testosterone concentrations for at least 180 but not 240 min. The time course for the reversal of the change in serum testosterone concentrations following SL-DIOL intake is very similar to the time course for sublingual testosterone intake (Stuenkel et al 1991;Salehian et al 1995). The intake of a fat containing meal results in reduced serum testosterone concentrations for »8 h, perhaps due to enhanced androgen uptake by the androgen receptor (Volek et al 2001).…”

“…In addition, acute EX does not alter the hormonal response to SL-DIOL intake. These Wndings are noteworthy as they demonstrate that, in contrast to ingesting 200 mg androstenediol (Earnest et al 2000) yet similar to sublingual testosterone intake (Salehian et al 1995;Stuenkel et al 1991), SL-DIOL promotes a transient change in serum hormone concentrations further demonstrating that sublingual administration of a small dose of testosterone precursors produces a more signiWcant acute response than does ingestion of larger doses. Additionally, in contrast to androstenedione ingestion (Ballantyne et al 2000), EX does not cause an exaggerated estradiol response to SL-DIOL intake.…”

A Comparison of a Novel Testosterone Bioadhesive Buccal System, Striant, with a Testosterone Adhesive Patch in Hypogonadal Males

“…Testosterone levels rose to within the normal range and improved scores in sexual function were achieved, although the duration of the increased testosterone level after the application of the system was rather short (2-4 h) (21). A sublingual preparation, cyclodextrin testosterone, has also been tested in the past, but limited experience is available with this preparation (22). More recently, three doses of a buccal preparation were tested on healthy volunteers pretreated with gonadotropin agonist, and favorable hormone profiles were achieved (23).…”

Testosterone Hormone Replacement Therapy: State-of-the-Art and Emerging Technologies

“…Each route of administration produces a distinct pharmacokinetic profile, the biological significance of which is not fully appreciated. Recently, a variety of additional methods for testosterone administration, including intramuscular therapy (86), nasal and pulmonary delivery, sublingual tablets (87), and topical aerosols (88,89), have been investigated in an attempt to overcome some perceived drawbacks with existing approaches.…”