The inhibition of human prostatic aromatase activity by imidazole drugs including ketoconazole and 4-hydroxyandrostenedione.

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Ayub M, Levell MJ

The inhibition of human prostatic aromatase activity by imidazole drugs including ketoconazole and 4-hydroxyandrostenedione.

Biochem Pharmacol. 1990 Oct 1;40(7):1569-75. doi: 10.1016/0006-2952(90)90456-u.

PubMed ID

2222512 [ View in PubMed

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Abstract

Ketoconazole, an orally active imidazole drug and bifonazole, clotrimazole, econazole, isoconazole, miconazole and tioconazole are known as inhibitors of cytochrome P450 dependent steroidogenic enzymes including human placental aromatase. The aim of the present study was to investigate the effectiveness of these imidazole drugs to inhibit human prostatic aromatase activity compared with the known inhibitor of aromatase 4-hydroxyandrostenedione (4-OHA). The imidazole drugs and 4-OHA inhibited prostatic aromatase activity in a dose-dependent manner. The order of decreasing inhibitory potency determined from IC50 values (mumol/L) was: 4-OHA (1.57) greater than bifonazole (1.6) greater than tioconazole (1.69) greater than clotrimazole (1.73) greater than econazole (1.87) greater than miconazole (2.0) greater than isoconazole (2.2) greater than ketoconazole (4.7). The IC50 values for the inhibition of prostatic homogenate aromatase activity are 3-9-fold higher than that for the inhibition of human placental aromatase activity, previously reported, except that of ketoconazole which was 1.5-fold lower than that for the inhibition of placental microsomal aromatase.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Econazole	Cytochrome P450 19A1	Protein	Humans	No	Inhibitor	Details
Tioconazole	Cytochrome P450 19A1	Protein	Humans	Unknown	Inhibitor	Details