CAS: 166526-99-4; 3-Hydroxy Agomelatine

上下游产品

agomelatine N-[2-(3,7-dihydroxy-1-naphthyl)ethyl]acetamide

📜阿戈美拉汀置于human Liver Cytochrome P450体系中,用 甲醇,Acetate Buffer 用作溶剂,化学反应生成N-(2-(7-羟基萘-1-基)乙基)乙酰胺,1'-Hydroxy-Agomelatine,阿戈美拉汀杂质,N-[2-(3,7-Dihydroxy-1-Naphthyl)Ethyl]Acetamide
参考文献:Prediction Of Interindividual Variation In Drug Plasma Levels In Vivo From Individual Enzyme Kinetic Data And Physiologically Based Pharmacokinetic Modeling
标题:Prediction Of Interindividual Variation In Drug Plasma Levels In Vivo From Individual Enzyme Kinetic Data And Physiologically Based Pharmacokinetic Modeling
摘要:A Strategy Is Presented To Predict Interindividual Variation In Drug Plasma Levels In Vivo By The Use Of Physiologically Based Pharmacokinetic Modeling And Human In Vitro Metabolic Parameters,Obtained Through The Combined Use Of Microsomes Containing Single Cytochrome P450 Enzymes And A Human Liver Microsome Bank. The Strategy,Applied To The Pharmaceutical Compound (N-[2-(7-Methoxyl-Naphtyl)-Ethyl]Acetamide),Consists Of The Following Steps: (1) Estimation Of Enzyme Kinetic Parameters K-M And V-Max For The Key Cytochrome P450 Enzymes Using Microsomes Containing Individual P450 Enzymes; (2) Scaling-Up Of The V-Max Values For Each Individual Cytochrome P450 Involved Using The Ratio Between Marker Substrate Activities Obtained From The Same Microsomes Containing Single P450 Enzymes And A Human Liver Microsome Bank; (3) Incorporation Into A Physiologically Based Pharmacokinetic Model. For Validation,Predicted Blood Plasma Levels And Pharmacokinetic Parameters Were Compared To Those Found In Human Volunteers: Both The Absolute Plasma Levels As Well As The Range In Plasma Levels Were Well Predicted. Therefore,The Presented Strategy Appears To Be Promising With Respect To The Integration Of Interindividual Differences In Metabolism And Prediction Of The Possible Impact On Plasma And Tissue Concentrations Of Drugs In Humans. (C) 2000 Elsevier Science B.V. All Rights Reserved.
Doi:10.1016/s0928-0987(00)00146-9