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The non-steroidal selective estrogen receptor modulator (SERM) tamoxifen (tam) is widely used in the treatment of breast cancer.SERMs are competitive inhibitors in the binding of estradiol to the ER.They may have estrogen or anti-estrogen activity depending on target tissue.Some of the estrogen agonistic effects of tam may cause serious complications such as thromboembolic disease and endometrial cancer.The metabolism of tam is complex and shows considerable inter-individual variation.Tam is considered a pro-drug and its bioconversion involves N-oxidation, Ndemethylation, and hydroxylation.Cytochrome P450 (CYP) 2D6 hydroxylates tam and Ndesmethyltam to the potent metabolites 4-hydroxytamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen).CYP2D6 has a polymorphic distribution that divides populations into"slow" or"rapid" metabolizers.Tam and its metabolites are furthermore conjugated and inactivated by polymorphic distributed UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs).CYP, SULT and UGT genotypes may influence treatment outcome during tam therapy.