The interaction of representative members from two classes of antimycotics—the azoles and the allylamines—with cytochromes P-450 in steroidogenic tissues and liver

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Abstract
1. Spectrophotometric studies with ketoconazole, clotrimazole and miconazole show strong type-II interactions with several cytochromes P-450, particularly (Ks107M−1; pH 7.4; 25.C) with the 11β-hydroxylase of adrenal mitochondria, with the 17α/20 lyase of testis microsomes and with some forms of cytochromes P-450 of liver. 2. A tight binding of the azoles also occurs to the reduced cytochromes, giving rise to an impeded CO binding to the haem iron. 3. The binding of the azoles to 11β-hydroxylase and 17α/20 lyase is much tighter than the binding of endogenous substrates, and consequently inhibition of steroidogenesis will occur at these sites. The metabolism of xenobiotic substrates by the cytochromes P-450 of liver will also be severely impeded. 4. In contrast, the allylamines naftifine and SF 86–327 are type-I substrates for a small portion of cytochromes P-450 of liver microsomes only and there is no spectral evidence for binding to the cytochromes P-450 involved in steroid biosynthesis.