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.
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"Raloxifene". Drug Information Portal. U.S. National Library of Medicine. "Raloxifene hydrochloride". Drug Information Portal. U.S. National Library of Medicine.