Nafarelin acetate is a gonadotropin-releasing hormone (GnRH) agonist which is as effective as danazol in the treatment of endometriosis. Its mechanism of action is that the desensitization of the pituitary GnRH receptor leads to a decrease in gonadotropin release, and the serum concentration of ovarian hormone is similar to that in postmenopausal women. Nafarelin reduces or eliminates physical symptoms associated with endometriosis, and the pregnancy rate after treatment with this drug is comparable to the pregnancy rate after danazol treatment. Nafarelin is treated by nasal inhalation and is generally well tolerated.
After nasal inhalation, nafarelin acetate is combined with GnRH receptor. Initially, it causes the release of gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland; however, long-term stimulation of the GnRH receptor results in the receptor desensitization and reduces the secretion of FSH and LH. For women, inhibiting gonadotropin secretion can lead to hypogonadism, resulting in decreased estrogen and progesterone secretion and reduced ovulation. For men, the inhibition of LH secretion will prevent testicular cells from secreting and releasing testosterone in the testicles, leading to a significant decrease in testosterone production, close to the post castrated level.
Nafarelin acetate is a widely used therapy for the treatment of central precocious puberty (CPP) in both sexes. The diagnosis of CPP should be confirmed by the response of pubic gonadotropin level and pubic LH to natural GnRH stimulation. Pelvic ultrasonography of girls usually indicates enlargement of the uterus and ovaries, often accompanied by polycystic formation. Other causes of early puberty, such as congenital adrenal hyperplasia, testosterone poisoning, testicular neoplasms and other autonomic feminization or masculinization disorders, must be excluded by appropriate clinical hormone and diagnostic imaging examinations.
Pharmacokinetics and metabolism
After an intravenous injection of nafarelin acetate, most of the radioactive materials disappear in the urine. There are five major radioactive urinary metabolites. Four of them are short peptides: 5-10-hexapeptide amide, 6-10-pentapeptide amide, 5-7-tripeptide, and 6-7-dipeptide; and the fifth metabolite is 2-naphthylacetic acid. It is possible to be formed by oxidative deamination of 3-(2-napthyl)-D-Ala to give the corresponding alpha-keto acid, then oxidative decarboxylation of the alpha-keto acid occurs. The five metabolites are added together in an amount greater than half of the given dose of radioactivity.
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