It is excreted mainly in the form of metabolites, with only trace amounts of the parent compound identified.The medication has an elimination half-life of about 8 hours or of 6 to 10 hours. Its half-life is shorter than that of other orexin receptor antagonists such as suvorexant (12 hours) and lemborexant (~18–55 hours). The relatively short half-life of daridorexant may allow for reduced daytime sedation. The duration of action of daridorexant in terms of sedative effects is approximately 8 hours with a 50 mg dose. Chemistry
Daridorexant is a small-molecule compound. The chemical name of daridorexant is (S)-(2-(5-chloro-4-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone. Its molecular formula is C23H23N6O2Cl and its molecular weight is 450.93 g/mol (or 487.38 g/mol for the hydrochloride). Daridorexant hydrochloride is a white to light yellowish powder and is very slightly soluble in water. History
Daridorexant was patented in 2013 and was first described in the scientific literature in 2017. It was approved for medical use in the United States in January 2022 and became available in this country in May 2022. On 24 February 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Quviviq, intended for the treatment of insomnia. On 29 April 2022, daridorexant was authorized for use in the European Union. It was the first orexin receptor antagonist to become available for use in the European Union. (The earlier orexin receptor antagonists suvorexant and lemborexant are not available in the European Union.)
The incidence of the syndrome is 1:14,025 with an equal sex distribution. It is determined by the autosomal dominant familial polyposis coli gene (APC) on chromosome 5.Gardner syndrome can be identified based on oral findings, including multiple impacted and supernumerary teeth, multiple jaw osteomas that give a "cotton-wool" appearance to the jaws, as well as multiple odontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE), in addition to multiple adenomatous polyps of the colon. Gardner syndrome is also associated with familial adenomatous polyposis and may manifest as aggressive fibromatosis (desmoid tumors) of the retroperitoneum.Desmoid tumors arise most frequently from the aponeurosis of the rectus abdominal muscle of multiparous women. The extra-abdominal form is rare and desmoids of the breast may arise in the mammary gland or may occur as an extension of a lesion arising from the muscles of the chest wall. The incidence of mammary desmoid tumors is less than 0.2% of primary breast neoplasms. In Gardners syndrome, the incidence ranges from 4% to 17%. Desmoid tumors associated with Gardners syndrome have been shown to have an alteration of the β-catenin pathway and over express β-catenin. Treatment
There is no cure for Gardner Syndrome. Treatments focus on alleviating symptoms and reducing risk of cancer. Treatments for desmoid tumors may include surgery, NSAIDS, anti-estrogen medications, radiation therapy and chemotherapy. Eponym
The syndrome is named for Eldon J. Gardner (1909–1989), a geneticist who first described it in 1951.