Both raloxifene and its glucuronide metabolites show high plasma protein binding (>95%), including to both albumin and α1 acid glycoprotein, but not to sex hormone-binding globulin. More specifically, raloxifene is 98.2 ± 0.4% bound to plasma proteins. Metabolism
Raloxifene is metabolized in the liver and undergoes enterohepatic recycling. It is metabolized exclusively by glucuronidation and is not metabolized by the cytochrome P450 system. Less than 1% of radiolabeled material in plasma comprises unconjugated raloxifene. The metabolites of raloxifene include several glucuronides. The elimination half-life of raloxifene after a single dose is 27.7 hours (1.2 days), whereas its half-life at steady state at a dosage of 60 mg/day is 15.8 to 86.6 hours (0.7–3.6 days), with an average of 32.5 hours (1.4 days). The extended half-life of raloxifene is attributed to enterohepatic recirculation and its high plasma protein binding. Raloxifene and its glucuronide conjugates are interconverted by reversible metabolism and enterohepatic recycling, which prolongs the elimination half-life of raloxifene with oral administration. The medication is deconjugated into its active form in a variety of tissues, including liver, lungs, spleen, bone, uterus, and kidneys. Elimination
Raloxifene is mainly excreted in bile and is eliminated in feces. Less than 0.2% of a dose is excreted unchanged in urine and less than 6% of a dose is excreted in urine as glucuronide conjugates. Chemistry
Raloxifene hydrochloride has the empirical formula C28H27NO4S•HCl, which corresponds to a molecular weight of 510.05 g/mol.
Cholesterol embolism occurs when cholesterol is released, usually from an atherosclerotic plaque, and travels as an embolus in the bloodstream to lodge (as an embolism) causing an obstruction in blood vessels further away. Most commonly this causes skin symptoms (usually livedo reticularis), gangrene of the extremities and sometimes kidney failure; problems with other organs may arise, depending on the site at which the cholesterol crystals enter the bloodstream. When the kidneys are involved, the disease is referred to as atheroembolic renal disease. The diagnosis usually involves biopsy (removing a tissue sample) from an affected organ. Cholesterol embolism is treated by removing the cause and giving supportive therapy; statin drugs have been found to improve the prognosis. Signs and symptoms
The symptoms experienced in cholesterol embolism depend largely on the organ involved. Non-specific symptoms often described are fever, muscle ache and weight loss. Embolism to the legs causes a mottled appearance and purple discoloration of the toes, small infarcts and areas of gangrene due to tissue death that usually appear black, and areas of the skin that assume a marbled pattern known as livedo reticularis. The pain is usually severe and requires opiates. If the ulcerated plaque is below the renal arteries the manifestations appear in both lower extremities.