CAS: 75524-31-1; 5-Hydroxymethylflucloxacillin

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Flucloxacillin sodium floxacillin

📜氟氯西林置于glucose-6-Phosphate Dehydrogenase,Glucose-6-Phosphate,Bacillus Megaterium Cyp102A1 M11 L437E,还原型辅酶ii(Nadph)四钠盐体系中,用 Aq. Phosphate Buffer,二甲基亚砜 作为反应溶剂,化学反应 20.0H,反应生成 5-羟基甲基氟氯西林
参考文献:Characterization Of Kinetics Of Human Cytochrome P450S Involved In Bioactivation Of Flucloxacillin: Inhibition Of Cyp3A-Catalysed Hydroxylation By Sulfaphenazole
标题:Characterization Of Kinetics Of Human Cytochrome P450S Involved In Bioactivation Of Flucloxacillin: Inhibition Of Cyp3A-Catalysed Hydroxylation By Sulfaphenazole
摘要:Background And Purposethe Aim Of This Study Was To Characterize The Human Cytochrome P450S (Cyps) Involved In Oxidative Bioactivation Of Flucloxacillin To 5‐hydroxymethyl Flucloxacillin,A Metabolite With High Cytotoxicity Towards Biliary Epithelial Cells.Experimental Approachthe Cyps Involved In Hydroxylation Of Flucloxacillin Were Characterized Using Recombinant Human Cyps,Pooled Liver Microsomes In The Presence Of Cyp‐specific Inhibitors And By Correlation Analysis Using A Panel Of Liver Microsomes From 16 Donors.Key Resultsrecombinant Cyps Showing The Highest Specific Activity Were Cyp3A4,Cyp3A7 And To Lower Extent Cyp2C9 And Ctp2C8. Michaelis-menten Enzyme Kinetics Were Determined For Pooled Human Liver Microsomes,Recombinant Cyp3A4,Cyp3A7 And Cyp2C9. Surprisingly,Sulfaphenazole Appeared To Be A Potent Inhibitor Of 5'‐hydroxylation Of Flucloxacillin By Both Recombinant Cyp3A4 And Cyp3A7.Conclusions And Implicationsthe Combined Results Show That The 5'‐hydroxylation Of Flucloxacillin Is Primarily Catalysed By Cyp3A4,Cyp3A7 And Cyp2C9. The Large Variability Of The Hepatic Expression Of These Enzymes Could Affect The Formation Of 5'‐hydroxymethyl Flucloxacillin,Which May Determine The Differences In Susceptibility To Flucloxacillin‐induced Liver Injury. Additionally,The Strong Inhibition In Cyp3A‐catalysed Flucloxacillin Metabolism By Sulfaphenazole Suggests That Unanticipated Drug-drug Interactions Could occur With Coadministered Drugs.
DOI:10.1111/bph.14548