生理藥理學(xué)(5,6章)

1、Drug at site of administrationDrug and/or metabolite(s)in urine, feces, bileDrug in tissues 3. MetabolismMetabolite(s) in tissue游離型藥物游離型藥物血液循環(huán)血液循環(huán)結(jié)合型藥物結(jié)合型藥物藥物藥物吸收吸收靶組織靶組織游離結(jié)合游離結(jié)合其它組織其它組織游離結(jié)合游離結(jié)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. ）給藥途徑與血藥濃度的關(guān)系給藥途徑與血藥濃度的關(guān)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藥酶藥酶藥酶藥酶選擇性低，特異性不強；選擇性低，特異性不強；可被飽和；可被飽和； 個體差異大；個體差異大； 可被藥物誘導(dǎo)或抑制。可被藥物誘導(dǎo)或抑制。環(huán)氧芳香產(chǎn)物：環(huán)氧芳香產(chǎn)物：抗原性；引起抗原性；引起肝壞死，核酸肝壞死，核酸突變突變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 （異煙肼）后的血濃（異煙肼）后的血濃Portal circulationLivergall bladderGutBile ductDrugBiotransformat