Lønning P E, Johannessen D C, Thorsen T
Department of Therapeutic Oncology and Radiophysics, University of Bergen, Norway.
Br J Cancer. 1989 Jul;60(1):107-11. doi: 10.1038/bjc.1989.231.
Plasma level, plasma clearance, production rate and interconversions of oestrone and oestrone sulphate were measured in six breast cancer patients receiving aminoglutethimide therapy. Three additional patients had the production rate of oestrone sulphate investigated. Plasma oestrone and oestrone sulphate levels were reduced by a mean of 46% (P less than 0.05) and 71% (P less than 0.005) respectively. These alterations were due to a combined action of aminoglutethimide inhibiting oestrogen production but also increasing oestrogen metabolism. While oestrone and oestrone sulphate production rate was reduced by a mean of 31% (P less than 0.05) and 41% (P less than 0.005) respectively, the plasma clearance rate of oestrone was found to be increased by a mean of 30% (P less than 0.05), and the plasma clearance rate of oestrone sulphate was increased by a mean of 112% during aminoglutethimide treatment. The fraction of oestrone sulphate converted into plasma oestrone was reduced by 52% (P less than 0.05), the transfer of circulating oestrone into sulphate was non-significantly reduced by a mean of 16%. The findings in this investigation show that aminoglutethimide treatment influences oestrogen disposition by mechanisms unrelated to aromatase inhibition. The possibility that such effects might be partly responsible for the mechanism of action of aminoglutethimide in advanced breast cancer should be considered.
对6例接受氨鲁米特治疗的乳腺癌患者测定了雌酮和硫酸雌酮的血浆水平、血浆清除率、生成率及相互转化情况。另外3例患者对硫酸雌酮的生成率进行了研究。血浆雌酮和硫酸雌酮水平分别平均降低了46%（P<0.05）和71%（P<0.005）。这些改变是由于氨鲁米特抑制雌激素生成同时增加雌激素代谢的联合作用所致。虽然雌酮和硫酸雌酮生成率分别平均降低了31%（P<0.05）和41%（P<0.005），但在氨鲁米特治疗期间，雌酮的血浆清除率平均增加了30%（P<0.05），硫酸雌酮的血浆清除率平均增加了112%。硫酸雌酮转化为血浆雌酮的比例降低了52%（P<0.05），循环雌酮向硫酸盐的转化平均非显著降低了16%。本研究结果表明，氨鲁米特治疗通过与芳香化酶抑制无关的机制影响雌激素的处置。应考虑这种效应可能部分解释氨鲁米特在晚期乳腺癌中作用机制的可能性。
