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Objective To determine whether the cytochrome P4502B6(CYP2B6)is involved in the oxidation of propofol by human liver microsomes.Methods The change of propofol concentration in an incubation mixture with human liver microsomes was monitored by the high performance liquid chromatography(HPLC),in order to calculate the rate constants of metabolism of propofol.The correlation between the rate constants and the rate of metabolism of CYP2B6 selective substrate bupropion,and the effect of two different CYP2B6 specific inhibitors on the propofol metabolism were examined.Results The mean rate constant of propofol metabolism by liver microsomes obtained from twelve individuals was 3.9(95% confidence intervals 3.3,4.5)nmol·min-1·mg-1 protein.The rate constants of propofol metabolism by liver microsomes were significantly correlated with bupropion hydroxylation(r=0.888,P<0.001).Both selective chemical inhibitors of CYP2B6,orphenadrine and N,N’,N″-triethylenethiophosphoramide(thioTEPA),reduced the rate constants of propofol metabolism by 37.5%(P<0.001)and 42.7%(P<0.001)in liver microsomes,respectively.Conclusions CYP2B6 is predominantly involved in the oxidation of propofol by human liver microsomes.
Objective To determine whether the cytochrome P4502B6 (CYP2B6) is involved in the oxidation of propofol by human liver microsomes. Methods The change of propofol concentration in an incubation mixture with human liver microsomes was monitored by the high performance liquid chromatography (HPLC), in order to calculate the rate constants of metabolism of propofol.The correlation between the rate constants and the rate of metabolism of CYP2B6 selective substrate bupropion, and the effect of two different CYP2B6 specific inhibitors on the propofol metabolism were observed. Results The mean rate constant of propofol metabolism by liver microsomes obtained from two individuals was 3.9 (95% confidence intervals 3.3, 4.5) nmol · min-1 · mg-1 protein.The rate constants of propofol metabolism by liver microsomes were significantly correlated with bupropion hydroxylation (r = 0.888, P <0.001). Both selective chemical inhibitors of CYP2B6, orphenadrine and N, N ’, N "-triethylenethiophosphoramide (thioTEPA), reduced the rate constants of propofol metabolism by 37.5% (P <0.001) and 42.7% (P <0.001) in liver microsomes, respectively.Conclusions CYP2B6 is predominantly involved in the oxidation of propofol by human liver microsomes.