Liarozole (R 75251, R75,251) is an orally active benzimidazole-based retinoic acid (RA) metabolism blocking agent (RAMBA) th at targets multiple P450 enzymes, including aromatase (CYP19), 17-hydroxylase/17,20-lyase (CYP17A1), 11-hydroxylase (CYP11B1), and RA 4-hydroxylase (CYP26). Liarozole is more effective than ketoconazole in vivo (plasma RA enhancement = 2.5 ng/mL vs. 1.3 ng/mL 2 hr after respective oral dosage of 40 mg/kg in rats) and, in contrast to ketoconazole, Liarozole does not significantly affect circulating adrenal androgen levels. Liarozole is shown to effectively suppress androgen-dependent tumor expansion of R3327G Dunning prostate adenocarcinoma xenografts in rats (by 66% and 81% with 80 and 120 mg/kg/day p.o., respectively) independent of its androgen biosynthesis inhibition.
