Testosterone, undecanoate

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Danger

H302 (93.3%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P263, P264, P270, P271, P280, P301+P317, P302+P352, P304+P340, P317, P318, P321, P330, P362+P364, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 45 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Once in circulation, testosterone undecanoate is cleaved to release testosterone, which mediates a range of biological actions. Testosterone is an endogenous male hormone that plays a key role in male sexual differentiation: it is involved in the regulation of hematopoiesis, body composition, and bone metabolism. As a hormone replacement therapy, testosterone undecanoate is an exogenous source of testosterone in males with hypogonadism. Testosterone therapy aims to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, and loss of muscle and bone mass. Testosterone has a controlled substance in the US due to the abuse potential by athletes and bodybuilders. The use of testosterone at higher doses than recommended can lead to withdrawal symptoms lasting for weeks or months. Withdrawal symptoms include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido, and hypogonadotropic hypogonadism. Testosterone can cause hirsutism, virilization, deepening of the voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities when administered to women. The use in adolescents can lead to the premature closure of bony epiphyses with termination of growth and precocious puberty.

Testosterone is a critical male sex hormone that is responsible for the normal growth and development of the male sex organs and the maintenance of secondary sex characteristics, such as the growth and maturation of male sex organs, the development of male hair distribution, vocal cord thickening, and alterations in body musculature and fat distribution. Male hypogonadism, resulting from insufficient testosterone secretion, has two main etiologies: primary hypogonadism is caused by defects in the gonads, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH and LH). In the circulation, testosterone undecanoate is cleaved by endogenous non-specific esterases to release testosterone, the active component of the compound. The undecanoate side chain is pharmacologically inactive. Testosterone can be further converted by 5α reductase to its more biologically active form, dihydrotestosterone (DHT). The actions of testosterone and DHT are mediated via androgen receptor, which is widely expressed in many tissues, including the bone, muscle, prostate, and adipose tissue. Testosterone binds to androgen receptors with high affinity and regulates target gene transcription involved in the normal growth and development of the male sex organs and the maintenance of secondary sex characteristics. Testosterone can cause improved sexual function, increased lean body mass, bone density, erythropoiesis, prostate size, and changes in lipid profiles.

The elimination half-life of testosterone undecanoate is approximately two hours. Once testosterone is formed from testosterone undecanoate, the half life of testosterone can vary and the reported values in the literature remain inconsistent, ranging from 10 to to 100 minutes. Testosterone undecanoate in castor oil for intramuscular injection had a half life of 33.9 days, allowing it to maintain serum levels in the normal range for over 6 weeks.

Testosterone undecanoate can be reduced to dihydrotestosterone undecanoate via 5α-reductase. In the circulation, the ester bond linking testosterone to the undecanoic acid is cleaved by endogenous non-specific esterases. Like all fatty acids, the undecanoic side chain undergoes β-oxidation to form acetyl coenzyme A (CoA) and, finally, propionyl CoA. Testosterone is metabolized to various 17-keto steroids through two different pathways to form major active metabolites, estradiol and dihydrotestosterone (DHT).

TESTOSTERONE UNDECANOATE

Androstanes [CS]; Androgen [EPC]; Androgen Receptor Agonists [MoA]

Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.

Testosterone undecanoate is a lipophilic molecule that is absorbed into the intestinal lymphatic system after oral administration. It is then released into the general blood circulation by the thoracic duct, thereby bypassing the portal circulation and first-pass metabolism in the liver, unlike endogenous testosterone. Following oral administration of 237 mg twice per day in males with hypogonadism, the mean (SD) Cmax was 1008 (581) ng/dL. Tmax is about five hours following oral administration. Decreased testosterone exposure was observed when administered without food. Following intramuscular administration of 750 mg testosterone undecanoate, serum testosterone concentrations reached a maximum after a median of seven days (range of four to 42 days), which then slowly declined. The mean (SD) Cmax was about 90.9 (68.8) ng/dL on the fourth day following injection of testosterone undecanoate. Steady-state serum testosterone concentration was achieved with the third injection at 14 weeks. At 42 days following the injection, testosterone undecanoate was nearly undetectable.

About 90% of a testosterone dose given intramuscularly is excreted in the urine as glucuronic and sulfuric acid-conjugates of testosterone or as metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver.

There is no information available.

While there is limited information available, an earlier study reports a metabolic clearance rate of 24.5 mL/min/kg for testosterone following oral administration of 25 mg testosterone and 40 mg testosterone undecanoate in women.