title: Intramuscular testosterone undecanoate: pharmacokinetic aspects of a novel testosterone formulation during long-term treatment of men with hypogonadism.
abstract: In an open-label, randomized, prospective trial, we investigated pharmacokinetics and several efficacy and safety parameters of a novel, long-acting testosterone (T) undecanoate (TU) formulation in 40 hypogonadal men (serum testosterone concentrations < 5 nmol/liter). For the first 30 wk (comparative study), the patients were randomly assigned to receive either 10 x 250 mg T enanthate (TE) im every 3 wk (n = 20) or 3 x 1000 mg TU im every 6 wk (loading dose) followed by 1 x 1000 mg after an additional 9 wk (n = 20). In a follow-up study, observation continued in those patients who completed the comparative part and opted for TU treatment (8 x 1000 mg TU every 12 wk in former TU patients and 2 x 1000 mg TU every 8 wk plus 6 x 1000 mg every 12 wk in former TE patients) for an additional 20-21 months. Here we report only the pharmacokinetic aspects of the new TU formulation for the first approximately 2.5 yr of treatment. At baseline, serum T concentrations did not significantly differ between the two study groups. In the TE group, mean trough levels of serum T were always less than 10 nmol/liter before the next injection, whereas in the TU group, mean trough levels of serum T were 14.1 +/- 4.5 nmol/liter after the first two doses (6-wk intervals) and 16.3 +/- 5.7 nmol/liter after the 9-wk interval at wk 30. The mean serum levels of dihydrotestosterone and estradiol also increased in parallel to the serum T pattern and remained within the normal range. In the follow-up study, the former TU patients (n = 20) received eight TU injections at 12-wk intervals, and the TE patients (n = 16) switched to TU and initially received two TU injections at 8-wk intervals (loading) and continued with six TU injections at 12-wk intervals (maintenance). This regimen resulted in stable mean serum trough levels of T (ranging from 14.9 +/- 5.2 to 16.5 +/- 8.0 nmol/liter) and estradiol (ranging from 98.5 +/- 45.2 to 80.4 +/- 14.4 pmol/liter). The present study has shown that 1000 mg TU injected into male patients with hypogonadism at 12-wk intervals is well tolerated and leads to T levels within normal ranges, using four instead of 17 or more TE injections per year. An initial loading dose of either 3 x 1000 mg TU every 6 wk at the beginning of hormone substitution or 2 x 1000 mg TU every 8 wk after switching from the short-acting TE to TU were found to be a adequate dosing regimens for starting of treatment with the long-acting TU preparation.
authors.affiliation: Klinik II und Poliklinik für Innere Medizin der Universität zu Köln, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schubert
authors.forename: T
authors.initials: T
authors.lastname: Minnemann
authors.forename: D
authors.initials: D
authors.lastname: Hübler
authors.forename: D
authors.initials: D
authors.lastname: Rouskova
authors.forename: A
authors.initials: A
authors.lastname: Christoph
authors.forename: M
authors.initials: M
authors.lastname: Oettel
authors.forename: M
authors.initials: M
authors.lastname: Ernst
authors.forename: U
authors.initials: U
authors.lastname: Mellinger
authors.forename: W
authors.initials: W
authors.lastname: Krone
authors.forename: F
authors.initials: F
authors.lastname: Jockenhövel
mesh_terms: D000293:Adolescent; D000328:Adult; D002626:Chemistry, Pharmaceutical; D004958:Estradiol / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy*; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; C010792:testosterone undecanoate