PHARMACOKINETICS, BIOEFFICACY, AND SAFETY OF SUBLINGUAL TESTOSTERONE CYCLODEXTRIN IN HYPOGONADAL MEN - COMPARISON TO TESTOSTERONE ENANTHATE- A CLINICAL RESEARCH-CENTER STUDY

We studied and compared the pharmacokinetics and bioefficacy of two do ses of sublingual testosterone cyclodextrin (SLT; 2.5 and 5.0 mg, admi nistered 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 3 60 min. The calculated half-lives were 60.3 +/- 7.5 and 68.8 +/- 5.0 m in after a single dose of 2.5 and 5.0 mg SLT, respectively. The mean a rea under curve (AUG) of serum T was computed over 20-day periods for the 3 treatment groups. The mean net AUC of serum T after TE administr ation was about 4- and 2-fold higher than that in the 2.5 and 5 mg gro ups over the last 20 days. Serum estradiol and dihydrotestosterone fol lowed the same pattern as serum T. Serum estradiol to T ratios decreas ed after T replacement in all 3 groups, whereas serum dihydrotestoster one to T ratios were not significantly changed by T treatment. Suppres sion of serum LH and FSH levels was more marked in the patients treate d with TE than in those given SLT. Similarly, serum sex hormone-bindin g globulin levels showed significant decreases with androgen replaceme nt only in the TE and SLT 5.0 mg range groups. There were no significa nt adverse effects based on comprehensive physical examinations, urea, electrolytes, and renal or liver function tests. Hematocrit levels in creased in the TE-treated group, but remained slightly lower than base line levels in the SLT groups. Serum high density lipoprotein choleste rol showed a small, but significant, decrease with time of treatment i n all groups. Despite the differences in the AUC of serum T levels ach ieved by different androgen replacement therapies, all patients showed significant improvements in sexual motivation and performance, with n o significant difference between the treatment groups. We conclude tha t SLT may be a useful addition to the currently available injectable a nd transdermal delivery systems for treatment of hypogonadal men. Beca use of the ease of administration, rapid reversibility of effects, and lower AUC of serum T levels achieved compared to those of TE injectio ns, SLT may be especially suitable for treatment of boys with delayed puberty and older men with androgen deficiency.