title: Effect of cefixime and cefdinir, oral cephalosporins, on cytochrome P450 activities in human hepatic microsomes.
abstract: The effects of two kinds of oral cephalosporins, cefixime and cefdinir, on cytochrome P450 (CYP) activities in human hepatic microsomes were investigated. Both cefixime and cefdinir at 2 mM concentration neither inhibited nor stimulated CYP1A1/2-mediated 7-ethoxyresorufin O-deethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated 7-benzyloxyresorufin O-debenzylation, CYP2C8/9-mediated tolbutamide methylhydroxylation, CYP2C19-mediated S-mephenytoin 4'-hydroxylation, CYP2D6-mediated bufuralol 1'-hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, CYP3A4-mediated nifedipine oxidation, or CYP3A4-mediated testosterone 6beta-hydroxylation. The free fractions of cefixime and cefdinir in the incubation mixture, which were measured by ultracentrifugation, were 86.1-93.8% and 94.1-97.8%, respectively. These results suggest that both cefixime and cefdinir would not cause clinically significant interactions with other drugs, which are metabolized by CYPs, via the inhibition of metabolism.
authors.affiliation: Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. toshiro_niwa@po.fujisawa.co.jp
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niwa
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Shiraga
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Kagayama
mesh_terms: D001711:Biotransformation; D000077525:Cefdinir; D020682:Cefixime / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*
chemical_list: D002511:Cephalosporins; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D020682:Cefixime; D000077525:Cefdinir