Affinity of Drugs for Cytochrome P-450 Determined by Inhibition of p-Nitrophenetole O-Deethylation by Rat Liver Microsomes

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Abstract
The rate of conversion of p-nitrophenetole by rat liver microsomes was studied. Inhibition of the reaction by CO and by SKF 525-A [proadifer hydrochloride] and the absolute dependence on NADPH and O2 indicate that cytochrome P-450 catalyzes the reaction. The apparent Km for O2 was 0.07 .mu.M. Cytochrome b5 seemed to be involved in the formation of p-nitrophenol. The effect on p-nitrophenol formation of drugs known to be involved in drug interaction in clinical practice was studied. There was a competitive inhibition by phenytoin, disulfiram and chloramphenicol; a mixed-type inhibition by isoniazid was observed.