Affinity of drugs for cytochrome P-450 determined by inhibition of p-nitrophenetole O-deethylation by rat liver microsomes

L Jørgensen, Torben Johansen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The rate of conversion of p-nitrophenetole to p-nitrophenol by rat liver microsomes was studied. Inhibition of the reaction by CO and by SKF 525A and the absolute dependence on NADPH and oxygen indicate that cytochrome P-450 catalyzes the reaction. The apparent Km for oxygen was 0.07 microM. Furthermore, 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 (inhibitor constant, Ki, 30 microM), disulfiram (Ki, 2 microM) and chloramphenicol (Ki, 20 microM), whereas a mixed-type inhibition by isoniazid was observed (Ki, 1,3 mM and Kii, 10,6 mM).
Original languageEnglish
JournalActa pharmacologica et toxicologica
Volume53
Issue number1
Pages (from-to)70-7
Number of pages8
ISSN0001-6683
Publication statusPublished - 1. Jul 1983

Keywords

  • Animals
  • Biotransformation
  • Carbon Monoxide
  • Chloramphenicol
  • Cytochrome P-450 Enzyme System
  • Disulfiram
  • Drug Interactions
  • Isoniazid
  • Kinetics
  • Male
  • Microsomes, Liver
  • Nitrobenzenes
  • Nitrophenols
  • Oxidation-Reduction
  • Phenytoin
  • Proadifen
  • Rats
  • Rats, Inbred Strains

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