Testosterone undecanoate API Manufacturers

General Description:

Testosterone undecanoate, identified by CAS number 5949-44-0, is a notable compound with significant therapeutic applications. Testosterone undecanoate is the ester prodrug of and has a mid-chain fatty acid at the carbon 17β position. It was developed via fatty acid esterification of testosterone in order to achieve orally administer testosterone. There are oral and intramuscular formulations available for testosterone undecanoate: both formulations are indicated for testosterone replacement therapy in adult males with hypogonadism. Testosterone is a critical male hormone that is responsible for the normal growth and development of the male sex organs and for the maintenance of secondary sex characteristics. Male hypogonadism, resulting from insufficient testosterone secretion, can result symptoms and signs of testosterone deficiency, such as decreased libido, erectile dysfunction, and loss of muscle and bone mass. Testosterone replacement therapy aims to restore the levels of testosterone, thereby improving symptoms and signs of testosterone deficiency.

Indications:

This drug is primarily indicated for: Testosterone undecanoate is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. These conditions include: - Congenital or acquired primary hypogonadism: testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone , luteinizing hormone ) above the normal range. - Congenital or acquired hypogonadotropic hypogonadism: gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range. Testosterone undecanoate is not used to treat age-related hypogonadism. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Testosterone undecanoate undergoes metabolic processing primarily in: 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). This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Testosterone undecanoate are crucial for its therapeutic efficacy: 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) C_max was 1008 (581) ng/dL. T_max 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) C_max 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. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Testosterone undecanoate is an important consideration for its dosing schedule: 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. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Testosterone undecanoate exhibits a strong affinity for binding with plasma proteins: About 40% of circulating testosterone is bound to sex hormone-binding globulin (SHBG) and about 2% of the drug remains unbound to plasma proteins. The rest is loosely bound to albumin and other plasma proteins. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Testosterone undecanoate from the body primarily occurs through: 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. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Testosterone undecanoate is distributed throughout the body with a volume of distribution of: There is no information available. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Testosterone undecanoate is a critical factor in determining its safe and effective dosage: 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. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Testosterone undecanoate exerts its therapeutic effects through: 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. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Testosterone undecanoate functions by: 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. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Testosterone undecanoate belongs to the class of organic compounds known as steroid esters. These are compounds containing a steroid moiety which bears a carboxylic acid ester group, classified under the direct parent group Steroid esters. This compound is a part of the Organic compounds, falling under the Lipids and lipid-like molecules superclass, and categorized within the Steroids and steroid derivatives class, specifically within the Steroid esters subclass.

Categories:

Testosterone undecanoate is categorized under the following therapeutic classes: Androgens, Androstanes, Androstenes, Androstenols, BCRP/ABCG2 Substrates, Cytochrome P-450 CYP2B6 Substrates, Cytochrome P-450 CYP2C19 Substrates, Cytochrome P-450 CYP2C8 Substrates, Cytochrome P-450 CYP2C9 Substrates, Cytochrome P-450 CYP3A Inducers, Cytochrome P-450 CYP3A Inhibitors, Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Inducers, Cytochrome P-450 CYP3A4 Inducers (strength unknown), Cytochrome P-450 CYP3A4 Inhibitors, Cytochrome P-450 CYP3A4 Inhibitors (strength unknown), Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 CYP3A5 Substrates, Cytochrome P-450 CYP3A7 Substrates, Cytochrome P-450 Enzyme Inducers, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Substrates, Drugs that are Mainly Renally Excreted, Fused-Ring Compounds, Gonadal Hormones, Gonadal Steroid Hormones, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, OAT3/SLC22A8 Inducers, OATP1B3 substrates, P-glycoprotein inhibitors, Steroids, Testosterone and derivatives, Testosterone Congeners, Thyroxine-binding globulin inhibitors. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Testosterone undecanoate include:

• Water Solubility:<1 mg/mL