Nebido Mechanism of Action

Pharmacotherapeutic group: Androgens, 3-oxoandrosten (4) derivatives. ATC code: G03B A03.
Pharmacology: Pharmacodynamics: Testosterone undecanoate is an ester of the naturally occurring androgen, testosterone. The active form, testosterone, is formed by cleavage of the side chain.
Pharmacokinetics: Absorption: Nebido is an intramuscularly administered depot preparation of testosterone undecanoate and thus circumvents the first-pass effect. Following intramuscular injection of testosterone undecanoate as an oily solution, the compound is gradually released from the depot and is almost completely cleaved by serum esterases into testosterone and undecanoic acid.
Distribution: In male serum, around 98% of circulating testosterone is bound to sex hormone-binding globulin (SHBG) and albumin. Only the unbound fraction of testosterone is considered biologically active. Following the intravenous infusion of testosterone in elderly men, the elimination half-life was approximately one hour and the apparent volume of distribution about 1.0 L/kg.
Metabolism: Testosterone which is generated by ester cleavage from testosterone undecanoate is metabolized and excreted the same way as endogenous testosterone.
Elimination: Testosterone undergoes extensive hepatic and extrahepatic metabolism. After the administration of radiolabeled testosterone, about 90% of the radioactivity appears in the urine as glucuronic and sulphuric acid conjugates and 6% appears in the feces after undergoing enterohepatic circulation. Urinary products include androsterone and etiocholanolone.
Steady-state conditions: Following repeated i.m. injection of 1000 mg testosterone undecanoate to hypogonadal men using an interval of 10 weeks between two injections, steady-state conditions were achieved between the 3rd and the 5th administration. Mean Cmax and Cmin values of testosterone at steady-state were about 42 and 17 nmol/l, respectively. Post-maximum testosterone levels in the serum decreased with a half-life of about 90 days, which corresponds to the release rate from the depot.
Toxicology: Preclinical safety data: Toxicological studies have not revealed other effects than those which can be explained based on the hormone profile of Nebido.
Testosterone has been found to be non-mutagenic in vitro using the reverse mutation model (Ames test) or hamster ovary cells. A relationship between androgen treatment and certain cancers has been found in studies on laboratory animals. Experimental data in rats have shown increased incidences of prostate cancer after treatment with testosterone.
Sex hormones are known to facilitate the development of certain tumours induced by known carcinogenic agents. The clinical relevance of the latter observation is not known.
Fertility studies in rodents and primates have shown that treatment with testosterone can impair fertility by suppressing spermatogenesis in a dose dependent manner.