Pharmacokinetics of selective estrogen receptor modulators.
Selective estrogen receptor modulators (SERMs) are a class of compounds used to treat and prevent breast cancer and osteoporosis. SERMs currently approved for use in patients include tamoxifen, toremifene and raloxifene. These compounds are well tolerated in patients, and the most common adverse effects experienced in patients undergoing SERM therapy include vasomotor symptoms such as hot flashes and vaginal discharge. New SERMs currently under development for use in the treatment and prevention of osteoporosis and breast cancer include ospemifene, a derivative of toremifene, and arzoxifene, a compound very similar in structure to raloxifene. SERMs are administered orally at doses ranging from 20 to 60 mg/day. Tamoxifen and toremifene have a bioavailability of approximately 100%, whereas that of raloxifene is only 2%. SERMs are very highly bound to plasma proteins (>95%). Tamoxifen and toremifene are metabolised by the cytochrome p450 enzyme system, and raloxifene is metabolised by glucuronide conjugation. The terminal elimination half-lives of these drugs range from 27.7 hours to 7 days. The pharmacokinetics of these compounds are affected in hepatically impaired patients, but not in renally impaired patients. SERMs have several potential drug interactions with other agents, such as warfarin, rifampicin (rifampin), cholestyramine and aromatase inhibitors.
Morello
Karla C
KC
Department of Internal Medicine, University of California, Davis, Sacramento, California 95817, USA.
Wurz
Gregory T
GT
DeGregorio
Michael W
MW
D000367:Age Factors; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018565:Food-Drug Interactions; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology; D008107:Liver Diseases / Q000378:metabolism / Q000503:physiopathology; D010024:Osteoporosis / Q000188:drug therapy / Q000517:prevention & control; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
D020845:Selective Estrogen Receptor Modulators