Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Merck Sharp & Dohme Limited, Hertford Road, Hoddesdon, Hertfordshire, EN11 9BU, UK
Pharmacotherapeutic group: Androgens
ATC code: G03BA03
Restandol Testocaps, after oral administration, delivers physiological amount of testosterone in the circulation. Treatment of hypogonadal men also results in a clinically significant rise of plasma concentrations of dihydrotestosterone and oestradiol, as well as a decrease of SHBG (sex hormone binding globulin). Treatment of males with primary (hypergonadotropic) hypogonadism results in a normalization of gonadotropin levels.
Endogenous androgens, principally testosterone, secreted by the testes and its major metabolite DHT, are responsible for the development of the external and internal genital organs and for maintaining the secondary sexual characteristics (stimulating hair growth, deepening of the voice, development of the libido); for a general effect on protein anabolism; for development of skeletal muscle and body fat distribution; for a reduction in urinary nitrogen, sodium, potassium, chloride, phosphate and water excretion.
Androgens are also responsible for the growth spurt of adolescence and for the eventual termination of linear growth and stimulate the production of red blood cells by enhancing erythropoietin production.
The effects of testosterone in some target organs arise after peripheral conversion of testosterone to oestradiol, which then binds to oestrogen receptors in the target cell nucleus e.g. the pituitary, fat, brain, bone and testicular Leydig cells.
Exogenous administration of androgens inhibits endogenous testosterone release. With large doses of exogenous androgens, spermatogenesis may be suppressed.
Restandol Testocaps must be taken with a normal meal or breakfast to ensure absorption. Food enhances the absorption of Restandol Testocaps: In healthy volunteers the AUC of testosterone was increased more than 12–fold compared with fasted conditions when Restandol Testocaps was taken with a normal meal. No differences were found in the AUC of testosterone when Restandol Testocaps was taken with a normal meal (containing 18.8 grams of fat) as compared to a high fat meal (containing 44.1 grams of fat). The absorption is about 7%. Following oral administration of Restandol Testocaps, an important part of the active substance testosterone undecanoate is co-absorbed with the lipophilic solvent from the intestine into the lymphatic system, thus circumventing the first pass inactivation by the liver.
From the lymphatic system testosterone undecanoate is released into the plasma. Single administration of 20-80 mg Restandol Testocaps to postmenopausal women leads to peak-levels of total plasma testosterone of approximately 1.5-2.0, 2.5-5.5 and 5.2-10.3ng/ml after a dose of 20, 40 and 80 mg Restandol Testocaps, respectively. These levels are reached approximately 5-6 h (tmax) after administration. Plasma testosterone levels remain elevated for at least 8 hours. In Japanese women the testosterone levels are about two fold higher.
During steady state after 28 days of administration plasma levels of total testosterone in hypogonadal men were increased after administration of 40 mg t.i.d, 40 b.i.d+80 mg, 80 mg b.i.d and 80 mg t.i.d. The dose of 80 mg b.i.d or 80 mg t.i.d. resulted in levels in the male physiological range for a considerable proportion of the time during the day. Testosterone and testosterone undecanoate display a high (over 97%) non-specific binding to plasma proteins and sex hormone binding globulin in in vitro tests.
In plasma and tissues testosterone undecanoate is hydrolyzed to yield the natural male androgen testosterone. Testosterone is further metabolized to dihydrotestosterone and oestradiol, which are further metabolized via the normal pathways.
Excretion mainly takes place via the urine as conjugates of etiocholanolone and androsterone.
Dose-linearity has been demonstrated for 20-240 mg/day.
Preclinical data with androgens in general reveal no special hazards for humans. Experimental data in rodents have shown testosterone can promote the development of certain tumours in hormone responsive tissues. In reproductive studies the use of androgens in different species has been demonstrated to result in virilisation of the external genitals of female fetuses.
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