药代动力学基本原理

•••••••••()•Concentration-timecurve(c-tcurve)•c-t•c-t••04812162004812(h)(mg/L)IVPOc-tc-t8.50.70.3ka04812024681012(h)(mg/L)C-T•c-t––•c-t––Da-dDadt=KaDanka-k0-kaDadDadt=dDadt=k0-CamdCadtVKCam=−+-dDadt=Daka••:•:•:•:100×=F•(ka):h-1)•(tka):tka=0.693/ka•(tmax):•(Cmax):•(bioavailability,F):(areaundercurveAUC)02468(h)(mg/L)TmaxCmaxAUCTmaxCmaxAUCAUC(areaundercurve)04812024681012(h)(mg/L)ivimpo20mg/kgt1/2=1.73h(bioavailability)•1•AUC(po)/AUC(iv)100%(1)––:•AUC()/AUC()100%•(compartmentmodel)¾¾•c-t•(1)0(2)0(3)0(4)00.11.010.0100.004812(h)(mg/L)0.11.010.0100.004812(h)(mg/L)C-TC-T•––•––(α)(β)•––(α)(β(γ)•––••volumeofdistributionVd=D0/C0LL/kgD0C0•0.6L/kg0.2L/kg0.08L/kg0.20.35L/kgDDT0.07L/kg•c-t••048121620024681012(h)(mg/L)0.40.2C-TD-dDdt=KeDnkedDdt=ke-CmdCdtVKCm=−+-dDdt=keD••:•:0204060801000.04.08.012.0(h)(mg/L)1101000.04.08.012.0(h)(mg/L)02040608010004812(h)(mg/L)0.11.010.0100.004812(h)(mg/L)02040608010004812(h)(mg/L)0.11.010.0100.004812(h)(mg/L)•()–––•()––•(Michaelis-Menten)–()–()(1)•(ke):h-1)•(tke):tke=0.693/ke•(clearance,Cl):(L/h,ml/min).CL=/CLו(t1/2):––––(t)R(t)=0.5(t/t1/2)•t1/21hr(0.25h);•t1/2=1~4hr(2h);•t1/2=4~8hr(SIZ6h);•t1/2=8~24hr(SMZ11h);•t1/224hr(36h);CL=ke×Vd