title: UGT1A1*28 polymorphism influences glucuronidation of bazedoxifene.
abstract: Bazedoxifene is used for the prevention and treatment of osteoporosis. After peroral application, bazedoxifene is metabolized by UDP-glucuronosyltransferases (UGTs) to bazedoxifene-4'-glucuronide (M4) and bazedoxifene-5-glucuronide (M5). It has already been shown that a relatively common UGT1A1*28 polymorphism can considerably affect raloxifene pharmacokinetics and pharmacodynamics. As pharmacokinetics of bazedoxifene and raloxifene are very similar, the influence of UGT1A1*28 polymorphism on metabolism of bazedoxifene was investigated by genotyped microsomes. Our results indicate an influence of UGT1A1*28 allele on the formation clearance of both bazedoxifene metabolites. The decreased metabolic clearance was most pronounced in microsomes from polymorphic homozygote (*28/*28) where a 7 to 10-fold lower metabolic clearance was observed for both metabolites compared to other genotypes. In conclusion, the significant UGT1A1*28 genotype effect on bazedoxifene intrinsic metabolic clearance indicates that this subject is worth further exploration in vivo and provides valuable information research in this field.
authors.forename: T Trdan
authors.initials: TT
authors.lastname: Lušin
authors.forename: A
authors.initials: A
authors.lastname: Mrhar
authors.forename: J
authors.initials: J
authors.lastname: Trontelj
mesh_terms: D005260:Female; D005838:Genotype; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020845:Selective Estrogen Receptor Modulators / Q000493:pharmacokinetics*; D000099148:UGT1A1 Enzyme
chemical_list: D020719:Glucuronides; D014453:Glucuronosyltransferase; D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; D000099148:UGT1A1 Enzyme; C447119:bazedoxifene