他莫昔芬及其代谢产物在乳腺癌患者中的稳态药代动力学。

The steady-state pharmacokinetics of tamoxifen and its metabolites in breast cancer patients.

作者信息

Soininen K, Kleimola T, Elomaa I, Salmo M, Rissanen P

出版信息

J Int Med Res. 1986;14(3):162-5. doi: 10.1177/030006058601400309.

Abstract

The steady-state pharmacokinetics of tamoxifen and its metabolites was studied in sixteen patients with advanced mammary cancer. Patients were randomized to receive tamoxifen given as Tamofen, Leiras, or as Nolvadex, ICI, 20 mg twice daily for 16 weeks in a cross-over study. Plasma and urine samples were analyzed during one dose interval (12 h) after treatment for 8 and 16 weeks. The concentrations of tamoxifen, N-desmethyltamoxifen, N,N-desdimethyltamoxifen, and metabolite Y were determined in plasma and the areas under the plasma level curves were calculated. 4-Hydroxytamoxifen was not found in plasma. In urine samples only tamoxifen and N-desmethyltamoxifen were above the detection limits even though metabolite Y was also analyzed after acid hydrolysis. There were no statistically significant differences in the concentrations of tamoxifen and its metabolites between the two preparations. The results of nonresponders did not differ from those of responders. Liver metastases had no effect on the metabolism of tamoxifen.

摘要

在16例晚期乳腺癌患者中研究了他莫昔芬及其代谢产物的稳态药代动力学。在一项交叉研究中，患者被随机分为接受以Tamofen（来乐士）形式给药的他莫昔芬或接受以Nolvadex（依西美坦）形式给药的他莫昔芬，剂量为每日2次，每次20mg，共16周。在治疗8周和16周后的一个给药间隔（12小时）内分析血浆和尿液样本。测定血浆中他莫昔芬、N-去甲基他莫昔芬、N,N-二去甲基他莫昔芬和代谢产物Y的浓度，并计算血浆水平曲线下的面积。血浆中未发现4-羟基他莫昔芬。在尿液样本中，即使在酸水解后也分析了代谢产物Y，但只有他莫昔芬和N-去甲基他莫昔芬高于检测限。两种制剂之间他莫昔芬及其代谢产物的浓度没有统计学上的显著差异。无反应者的结果与有反应者的结果没有差异。肝转移对他莫昔芬的代谢没有影响。