体外代谢清除率模型用于药物肝代谢过程研究-黄峰.ppt

Major: chinese traditional medicine Name: 黄峰 （ 2110948107） In vitro methods to predict metabolic clearance rate of Drugs hepatic metabolism Contents Preclinical prediction theory Mathematical Mode Accuracy study The problem to be solved   90% of medicines are mainly involved in the biological conversion of ——P450. The liver is the main organ of drug metabolism . In vitro model has been successfully used to predict in vivo studies of liver metabolism . Preclinical prediction theory Theoretical basis Premise:base in the hepatic metabolism The first step:Parameters obtained in vitro—intrinsic clearanc=Clint The seceond step:using SF change the Clint and then using the model and this result to Predict in vivo clearance. Iwatsubo T, Hirota N, Ooie T,et al.Pction of in vivo drug metabolism in the human l iver from inredi vitro metabolism data.[J].Pharmacol Ther, 1997, 73(2): 147. About CLint Michaelis-menten equation C drug《 Km Remember：Clear all the metabolites (1—1) CLint = Vmax / Km CLint = V0 / S When Metabolites is not clear General Process——Another method Drug half-life =T1/2 (1—2) CLint =0.693V/ T1/2 Relevant conversion factors — Scaling factors(SF) SF is a conversion factor. SF is used to translant Clint to the liver clearanc eg: In the liver microsomes experiment, SF ‘s value is often used containing 45 mg microsomal protein per gram of liver (Rats and human). Mathematical model There are three models using to predict in vivo clearance: Well-stirred model Parallel tube model Dispersion model These models can use the Clint to calculate the liver clearance Mathematical model Well-stirred model Or venous equilibrium model Free drug concentration in blood vessels is equal to the drug concentration in liver cells. Mathematical model Parallel tube model Concentration decreased Mathematical model Dispersion model More complic