Testosterone undecanoate is an ester of the natural androgen, testosterone. The active form, testosterone, is formed as a result of the cleavage of the side chain.
Testosterone is the most important androgen in the male body and is synthesized mainly in the testicles and, to a lesser extent, in the adrenal cortex.
Testosterone is responsible for the formation of male characteristics during intrauterine development, in early childhood, as well as during puberty, and subsequently for maintaining the male phenotype and androgen-dependent functions (for example, spermatogenesis, sex glands). Insufficient testosterone secretion leads to male hypogonadism, which is characterized by low serum testosterone concentrations. Symptoms associated with male hypogonadism include, but are not limited to, erectile dysfunction, decreased libido, fatigue, depressive moods, absence, underdevelopment, or regression of secondary sexual characteristics, and an increased risk of osteoporosis. Exogenous androgens are prescribed to increase insufficient levels of endogenous testosterone and reduce the symptoms of hypogonadism.
Depending on the target organ, the nature of the action of testosterone is mainly androgenic (for example, the prostate gland, seminal vesicles, testicular appendage) or protein-anabolic (muscles, bones, hematopoietic system, kidneys, liver).
The effects of testosterone in some organs occur after the peripheral conversion of testosterone to estradiol, which then binds to estrogen receptors in the nuclei of target cells (for example, the pituitary gland, adipose tissue, brain, bones, and testicular Leydig cells).
In men suffering from hypogonadism, the use of androgens reduces the body fat mass, increases the non-fat body mass, and also prevents bone loss. Androgens can improve sexual function, as well as have a positive psychotropic effect by improving mood.
Suction. Nebido ® is an intramuscular depot drug containing testosterone undecanoate. For this reason, the effect of the first passage is absent. After intravenous injection of an oil solution of testosterone undecanoate, it is gradually released from the depot and almost completely broken down by serum esterases into testosterone and undecanoic acid. The increase in serum testosterone concentrations relative to baseline values can be determined as early as the next day after the injection.
Distribution. In two separate studies, the average testosterone Cmax values of 24 and 45 nmol / L were determined, respectively, 14 and 7 days after a single intravenous injection of 1000 mg of testosterone undecanoate to men suffering from hypogonadism. Postmaximal testosterone levels decreased, with T1 / 2 being approximately 53 days.
About 98% of the circulating testosterone is bound in the blood serum to sex steroid binding globulin and albumin. Only the free fraction of testosterone is considered biologically active. After intravenous administration of testosterone to elderly men, the apparent Vd was determined at a level of approximately 1 l / kg.
Metabolism. Testosterone, which is formed from testosterone undecanoate as a result of the cleavage of the ether bond, is metabolized and excreted from the body in the same ways as endogenous testosterone. Undecanoic acid is metabolized by β-oxidation in the same way as other aliphatic carboxylic acids.
Output. Testosterone undergoes significant metabolism in the liver and beyond. After the introduction of labeled testosterone, about 90% of radioactivity is detected in the urine in the form of glucuronide and sulfate acid conjugates, and 6% after passing the intestinal-hepatic circulation is detected in the feces. Products detected in the urine include androsterone and etiocholanolone.
The equilibrium concentration. After repeated intravenous injections of 1000 mg of testosterone undecanoate to men suffering from hypogonadism, with an interval between injections of 10 weeks, the equilibrium concentration was reached between the 3rd and 5th injections. The average values of Cmax and Cmin of testosterone in the equilibrium state were about 42 and 17 nmol / L, respectively. Postmaximal serum testosterone levels decreased with a T1 / 2 of approximately 90 days, which corresponds to the rate of release of the substance from the depot.
Testosterone deficiency in primary and secondary hypogonadism in men (testosterone replacement therapy).
Method of administration and dosage
Nebido ® injection (in 1 amp. or fl. contains 1000 mg of testosterone undecanoate) is produced 1 time in 10-14 weeks. With this frequency of injections, sufficient testosterone levels are maintained, and no accumulation of the substance occurs.
The contents of the ampoule or vial should be injected immediately after opening. The injection should be made very slowly. Nebido ® can only be administered strictly in/m. It is necessary to carefully ensure that the injected substance does not enter the vessel.
Start of treatment. Before starting treatment, you should determine the amount of testosterone in the blood serum. The first interval between injections can be shortened, but it should be at least 6 weeks. Css at this dose is achieved quickly.
Individual treatment adjustment. At the end of the interval between injections, it is recommended to measure the concentration of testosterone in the blood serum. If its concentration is lower than normal, then this may indicate the need to reduce the interval between injections. At high concentrations, it should be considered whether it is appropriate to increase this interval. The interval between injections should remain within the recommended range of 10-14 weeks.
Special categories of patients
Children and teenagers. Nebido ® is not intended for use in children and adolescents, since no clinical studies have been conducted for it in men under the age of 18 (see "Special instructions").
Elderly patients. The limited data available do not indicate the need for dose adjustment in elderly patients (see "Special instructions").
Patients with impaired liver function. No official studies have been conducted in patients with impaired liver function. The use of Nebido ® is contraindicated in men with current or a history of liver tumors (see "Contraindications").
Patients with renal insufficiency. No official studies have been conducted in patients with renal insufficiency.
- hypersensitivity to the active substance or to any of the auxiliary components of the drug;
- the presence of androgen-dependent prostate or breast carcinoma in men;
- hypercalcemia associated with malignant tumors;
- liver tumors currently present or in the anamnesis.
- Nebido ® should not be used in women.
patients with apnea syndrome.