Due to bioaccumulation it works its way up through the food web and thus biomagnifies, resulting in high concentrations among populations of some species. Top predatory fish, such as tuna or swordfish, are usually of greater concern than smaller species. The US FDA and the EPA advise women of child-bearing age, nursing mothers, and young children to completely avoid swordfish, shark, king mackerel and tilefish from the Gulf of Mexico, and to limit consumption of albacore ("white") tuna to no more than 170 g (6 oz) per week, and of all other fish and shellfish to no more than 340 g (12 oz) per week. A 2006 review of the risks and benefits of fish consumption found, for adults, the benefits of one to two servings of fish per week outweigh the risks, even (except for a few fish species) for women of childbearing age, and that avoidance of fish consumption could result in significant excess coronary heart disease deaths and suboptimal neural development in children.Because the process of mercury-dependent sequestration of selenium is slow, the period between exposure to methylmercury and the appearance of symptoms in adult poisoning cases tends to be extended. The longest recorded latent period is five months after a single exposure, in the Dartmouth case (see History); other latent periods in the range of weeks to months have also been reported. When the first symptom appears, typically paresthesia (a tingling or numbness in the skin), it is followed rapidly by more severe effects, sometimes ending in coma and death.
This is intended to reduce the incidence and severity of menopausal symptoms such as hot flushes and decreased bone mineral density that are secondary to estrogen deficiency. Pharmacokinetics
A single 40-mg oral dose of relugolix has been found to result in peak levels of relugolix of 29 ng/mL (47 nmol/L) after 1.5 hours. Steady-state levels are reached within 7 days with 40 mg/day relugolix administration. There is an approximate 2-fold accumulation of relugolix by 2 weeks of continuous administration. Food diminishes the oral bioavailability of relugolix by about 50%.Relugolix is a substrate for P-glycoprotein, which may have a limiting effect on its absorption and distribution. The plasma protein binding of relugolix is approximately 68 to 71% over a concentration range of 0.05 to 5 μg/mL.Relugolix is not a substrate for CYP3A4. The elimination half-life of relugolix is 36 to 65 hours across a dosage range of 20 to 180 mg/day. There is moderate to high interindividual variability in systemic exposure to relugolix.Relugolix is excreted mainly in feces (83%) and to a small degree in urine (4%). Only about 6% of a dose of relugolix is excreted unchanged. Chemistry
Relugolix is a non-peptide, small-molecule compound, and is structurally distinct from GnRH analogues. It is an N-phenylurea derivative. History
Relugolix was first described in 2004. It superseded sufugolix (developmental code name TAK-013), which was developed by the same researchers. Relugolix was approved for the treatment of uterine fibroids in Japan on 8 January 2019.