RESUMO
<p><b>OBJECTIVE</b>To observe the metabolism-based interaction of diphenytriazol and flavone compounds.</p><p><b>METHODS</b>Flavone compounds kaempferol, isoharmnten and Elsholtzia blanda benth extract were chosen as the substrate of glucuronidation in the phase II metabolism. The metabolism was investigated in different rat liver microsome incubates pretreated with beta-naphthoflavone (BNF), diphenytriazol and tea oil (control). The concentrations of residual substrate were determined by HPLC. Quercetin and kaempferol were coincubated with diphenytriazol in control microsome to evaluate the inhibition for phase I metabolism. The concentration of diphenytriazol was determined by HPLC.</p><p><b>RESULT</b>The phase II metabolic activity of kaempferol, isoharmnten and Elsholtzia blanda benth extract in diphenytriazol-treated microsome was more potent than that in BNF-treated microsome (P<0.01). The phase I metabolism of diphenytriazol was markedly inhibited by quercetin and kaempferol, with the inhibition constants (Ki) (12.41 +/-0.26)microg . ml(-1) and (7.97 +/-0.08)microg . ml(-1), respectively.</p><p><b>CONCLUSION</b>Diphenytriazol demonstrates metabolism-based interaction with flavone compounds in vitro.</p>
Assuntos
Animais , Feminino , Ratos , Abortivos , Metabolismo , Farmacologia , Interações Medicamentosas , Flavonas , Metabolismo , Farmacologia , Quempferóis , Metabolismo , Farmacologia , Extratos Vegetais , Farmacologia , Quercetina , Metabolismo , Farmacologia , Ratos Sprague-Dawley , Triazóis , Metabolismo , FarmacologiaRESUMO
The paper summarizes the interactions between luteolin (glucosides) and drug-metabolizing enzyme from the literature of recent years and our research work. The metabolism of luteolin is chiefly mediated by phase II metabolic enzyme. Its glucosides are firstly hydrolyzed into aglycone in intestinal tract, and then absorbed and metabolized. Luteolin has the effect on the induction of CYP3A, and on the inhibition of CYPIA, 1B and 2E. Also, luteolin is an effective inhibitor of CYP2B6, CYP2C9 and CYP2D6. Luteolin can induce and inhibit UGTs and SULTs. It can also inhibit multi ABC transport proteins. Understanding the interactions between luteolin (glucosides) and drug-metabolizing enzyme has an important significance in guiding clinical use of the drug.