Wouters W, Snoeck E, De Coster R
Department of Endocrino- & Immunopharmacology, Janssen Research Foundation, Beerse, Belgium.
Breast Cancer Res Treat. 1994;30(1):89-94. doi: 10.1007/BF00682743.
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.
伏罗唑是一种新型三唑化合物的(+)-(S)-异构体，是一种强效且选择性的芳香化酶抑制剂。在体外，该化合物的活性比氨鲁米特高一千多倍。在体内，该化合物能非常有效地抑制卵巢、外周和肿瘤组织中的芳香化酶。与抑制其他细胞色素P450依赖性和非细胞色素P450依赖性反应相比，伏罗唑在体外对芳香化酶抑制的选择性优势为10000倍。这种选择性在大鼠体内得到了证实。伏罗唑与卵巢切除术一样，几乎能完全抑制大鼠二甲基苯并蒽诱导的乳腺癌模型中的肿瘤生长。在绝经后女性中，伏罗唑能非常有效地抑制雄烯二酮向雌酮的外周转化。长期给药后，血浆雌二醇水平降低，而肾上腺糖皮质激素和盐皮质激素水平保持不变。伏罗唑具有出色的口服生物利用度，并呈现线性、剂量成正比的药代动力学特征。
