Aromatase inhibition by R 83 842, the dextro isomer of R 76 713, in JEG-3 choriocarcinoma grown in ovariectomized nude mice

Vorozole, the (+)-(S)-isomer of a new triazole compound, is a potent and selective aromatase inhibitor. In vitro, the compound is over a thousandfold more active than aminoglutethimide. In vivo, the compound very potently inhibits ovarian, peripheral, and tumoral aromatase. Vorozole shows an in vitro selectivity margin of 10,000-fold for aromatase inhibition as compared to inhibition of other P450- and non-P450-dependent reactions. This selectivity was confirmed in the rat in vivo. Vorozole, like ovariectomy, almost completely reduces tumor growth in the DMBA-induced mammary carcinoma model in the rat. In postmenopausal women, vorozole very potently inhibits peripheral conversion of androstenedione to estrone. After chronic administration, plasma estradiol levels are reduced while the levels of adrenal gluco- and mineralo-corticoids remain unchanged. Vorozole has excellent oral bioavailability and exerts linear, dose-proportional pharmacokinetics.

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