生理药理学(5,6章)

1、Drug at site of administrationDrug and/or metabolite(s)in urine, feces, bileDrug in tissues 3. MetabolismMetabolite(s) in tissue游离型药物游离型药物血液循环血液循环结合型药物结合型药物药物药物吸收吸收靶组织靶组织游离结合游离结合其它组织其它组织游离结合游离结合Weak acidWeak baseH+HAA-HAH+A-BBH+H+H+BBH+The pH on each side of the membrane determines the equilibrium o

2、n each side extracellularpHintracellularpHlog= pKapHDoseDestroyed in gutNotabsorbed Destroyed by gut wallDestroyedby liverTosystemiccirculation100%100% AUC i.v.AUC oraltimeplasma concentration of drugBioavailability = AUC poAUC i.v.X 100AUC = area under the curveMSCMECback（As kidney function is redu

3、ced ，the serum creatinine level increases and also the kanamycin takes longer to be eliminated from the body. ）给药途径与血药浓度的关系给药途径与血药浓度的关系 1000 molecules % bound free99.990.0100 1100-fold increase in free pharmacologically active concentration at site of action.Effective TOXIC ThanksPortal venousbloods

4、ystemicarterialbloodbilevenous bloodHepatocytessmoothendoplasmicreticulummicrosomescontain cytochrome P450dependent mixed function oxidases药酶药酶药酶药酶选择性低，特异性不强；选择性低，特异性不强；可被饱和；可被饱和； 个体差异大；个体差异大； 可被药物诱导或抑制。可被药物诱导或抑制。环氧芳香产物：环氧芳香产物：抗原性；引起抗原性；引起肝坏死，核酸肝坏死，核酸突变突变0 1 2 3 Isoniazid conc. ug/ml 9 10 11 12 No. of patients 267位患者口服位患者口服 9.8 mg/kg isoniazid （异烟肼）后的血浓（异烟肼）后的血浓Portal circulationLivergall bladderGutBile ductDrugBiotransformat