DISTRIBUTION OF TAMOXIFEN AND METABOLITES INTO BRAIN-TISSUE AND BRAIN METASTASES IN BREAST-CANCER PATIENTS
DISTRIBUTION OF TAMOXIFEN AND METABOLITES INTO BRAIN-TISSUE AND BRAIN METASTASES IN BREAST-CANCER PATIENTS
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DOI：
10.1038/bjc.1991.147
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发表时间：
1991-04-01
影响因子：
8.8
通讯作者：
UELAND, PM
中科院分区：
文献类型：
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作者：
LIEN, EA;WESTER, K;UELAND, PM
我们测定了乳腺癌脑转移灶及其周围脑组织中他莫昔芬、N-去甲基他莫昔芬(代谢物X)、N-脱甲基他莫昔芬(代谢物Z)和羟化代谢物(Y、B、BX)的含量。标本来自三名乳腺癌患者，他们接受三苯氧胺治疗7-180天，最后一次剂量在手术切除肿瘤前28小时内服用。他莫昔芬及其代谢产物在脑转移瘤和脑组织中的浓度比血清中高出46倍。代谢物X含量最高，其次是他莫昔芬和代谢物Z。大多数样品中都检测到少量但相当数量的羟化代谢物trans-1(4-beta-hydroxyethoxyphenyl)-1，2-diphenylbut-1-ene(代谢物Y)、4-羟基-N-脱甲基他莫昔芬(代谢物B)和4-羟基-N-去甲基他莫昔芬(代谢物BX)。他莫昔芬在肿瘤、脑和血清中的浓度与各种代谢物的比例相似。这是首次报道他莫昔芬及其代谢物在人脑和脑瘤中的分布，为进一步研究他莫昔芬治疗乳腺癌脑转移的疗效奠定了基础。
We determined the amount of tamoxifen, N-desmethyltamoxifen (metabolite X), N-desdimethyltamoxifen (metabolite Z), and hydroxylated metabolites (Y, B, BX) in brain metastases from breast cancer and in the surrounding brain tissues. Specimens were collected from three breast cancer patients who received tamoxifen for 7-180 days and with the last dose taken within 28 h before surgical removal of the tumour. The concentrations of tamoxifen and its metabolites were up to 46-fold higher in the brain metastatic tumour and brain tissue than in serum. Metabolite X was the most abundant species followed by tamoxifen and metabolite Z. Small but significant amounts of the hydroxylated metabolites, trans-1(4-beta-hydroxyethoxyphenyl)-1,2-diphenylbut-1-ene (metabolite Y), 4-hydroxytamoxifen (metabolite B) and 4-hydroxy-N-desmethyltamoxifen (metabolite BX) were detected in most specimens. The ratios between the concentrations of tamoxifen and various metabolites were similar in tumour, brain and serum. This is the first report on the distribution of tamoxifen and metabolites into human brain and brain tumour, and the data form a basis for further investigation into the therapeutic effects of tamoxifen on brain metastases from breast cancer.