title: Testosterone buciclate (20 Aet-1) in hypogonadal men: pharmacokinetics and pharmacodynamics of the new long-acting androgen ester.
abstract: Due to unfavorable pharmacokinetics of the available androgen esters for substitution therapy of male hypogonadism, there is a demand for new testosterone (T) preparations producing constant serum levels in the physiological range. To assess the pharmacokinetics and pharmacodynamics of the new ester testosterone buciclate (TB) [20 Aet-1] in hypogonadal men a clinical phase I-study was performed. After two control examinations 8 male patients with primary hypogonadism were randomly assigned to 2 treatment groups (n = 2 x 4) given single doses of either 200 (group I) or 600 mg (group II) TB im. Blood samples were obtained 1, 2, 3, 5, and 7 days post injection and then weekly in the course of 4 months. In group I serum androgen levels did not rise to normal values. However, in group II androgens increased significantly and were maintained in the normal range up to 12 weeks with maximal serum levels of 13.1 +/- 0.9 nmol/L (mean +/- SE) in study week 6. No initial peak release of T was observed in either study group. Pharmacokinetic analysis revealed a terminal elimination t1/2 beta of 29.5 +/- 3.9 days and a mean residence time of 65.0 +/- 9.9 days in group II. In one patient in group II dihydrotestosterone levels slightly exceeded the upper normal limit during the study course. Sex hormone-binding globulin remained unchanged and estradiol serum levels never exceeded the normal range in any patient. In group II gonadotropins were significantly suppressed, whereas no change was seen in group I. A significant increase in body weight, hematological parameters, and libido/potency was observed after TB injection which was more pronounced in the higher dose group. Regardless of the dose administered, no significant change was seen in uroflow, prostate volume measured by transrectal ultrasonography, or prostate specific antigen. No adverse side-effects including changes in clinical chemistry were observed. In conclusion, single injections of 600 mg TB in hypogonadal patients show favorable pharmacokinetics and pharmacodynamics. This new long-acting T ester is a promising new agent for substitution therapy of male hypogonadism and for male contraception.
authors.affiliation: Institute of Reproductive Medicine of the University, Münster, Germany.
authors.forename: H M
authors.initials: HM
authors.lastname: Behre
authors.forename: E
authors.initials: E
authors.lastname: Nieschlag
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood; D001794:Blood Pressure; D001835:Body Weight; D004920:Erythropoiesis; D004967:Estrogens / Q000097:blood; D006062:Gonadotropins / Q000097:blood; D006400:Hematocrit; D006801:Humans; D007006:Hypogonadism / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000000981:diagnostic imaging / Q000187:drug effects; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D012725:Sexual Behavior / Q000187:drug effects; D013739:Testosterone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D014463:Ultrasonography
chemical_list: D000728:Androgens; D004967:Estrogens; D006062:Gonadotropins; D012738:Sex Hormone-Binding Globulin; C050320:testosterone 4-n-butylcyclohexylcarboxylic acid; D013739:Testosterone