Effects of Metronidazole, Azanidazole, and Azathioprine on Cytochrome P450 and Various Mono-Oxygenase Activities in Hepatic Microsomes from Control and Induced Mice

Drugs containing the imidazole ring have been reported to exert a potent inhibi­tory effect on microsomal mixed function mono-oxygenase (MFO) activity in man and experimental animals (Wilkinson et al. 1972; Pelkonen and Puurunen 1980; Murray 1984; Kapetanovic and Kupferberg 1984; Koop and Coon 1984; Kadderis and Rickert 1985; Horai et al. 1985). Such effects, mainly found in the liver and, recently, also in gonad and adrenal tissues (Mason et al. 1985), depend upon many factors. Species- and age-related differences have been established (Tu et al. 1981; Hajek and Novak 1982; Reinke et al. 1985). However, single or repeated administration of some imidazole derivatives was shown to result in an inhibition or an induction of MFO activity (Hajek and Novak 1982). By consider­ing the multiplicity of cytochrome (Cyt) P450 isoenzymes in microsomes, these conflicting results become understandable.