KETOCONAZOLE BLOCKS ADRENAL-STEROID SYNTHESIS
KETOCONAZOLE BLOCKS ADRENAL-STEROID SYNTHESIS
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DOI：
10.7326/0003-4819-97-3-370
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发表时间：
1982-01-01
影响因子：
39.2
通讯作者：
STEVENS, DA
中科院分区：
文献类型：
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作者：
PONT, A;WILLIAMS, PL;STEVENS, DA
酮康唑是一种口服的广谱抗真菌药物，可抑制真菌中甾醇的合成。当服用这种药物的一些患者出现男性乳房发育时，研究了酮康唑对人类和大鼠分离的肾上腺细胞类固醇合成的影响。在健康人中，皮质醇对ACTH的反应在400或600 mg剂量后4小时显著减弱。抑制持续长达8小时，并在16小时消失，表明肾上腺雄激素反应降低。很容易达到的治疗浓度的酮康唑几乎消除了皮质酮的生产从大鼠分离的肾上腺细胞。虽然目前使用的剂量的酮康唑从未被证明会引起临床肾上腺功能减退，但在高剂量或多剂量试验中应谨慎。该药物可用作阻断类固醇合成的药剂。
Ketoconazole, a broad-spectrum, antifungal drug that is administered orally, inhibits sterol synthesis in fungi. When gynecomastia developed in some patients taking this drug, the effects of ketoconazole on steroid synthesis were investigated in humans and in isolated adrenal cells from rats. In healthy humans, the cortisol response to ACTH was significantly blunted 4 h after a 400 or 600-mg dose. The inhibition persisted for up to 8 h and was absent by 16 h, indicating that adrenal androgen response was reduced. Easily achieved therapeutic concentrations of ketoconazole virtually eliminated corticosterone production by isolated adrenal cells from rats. Although ketoconazole at currently used doses has never been documented to cause clinical hypoadrenalism, caution is urged in high- or multiple-dose trials. The drug may be useful as an agent to block steroid synthesis.