Equivalent single-dose pharmacokinetics of two different dosing methods of prolonged-release fulvestrant ('Faslodex') in postmenopausal women with advanced breast cancer
Equivalent single-dose pharmacokinetics of two different dosing methods of prolonged-release fulvestrant ('Faslodex') in postmenopausal women with advanced breast cancer
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DOI：
10.1007/s00280-003-0643-7
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发表时间：
2003-10-01
影响因子：
3
通讯作者：
Harrison, MP
中科院分区：
文献类型：
--
作者：
Robertson, JFR;Harrison, MP
目的。比较氟维司群（“Faslodex”）两种不同给药方法的药代动力学，氟维司群是一种雌激素受体拮抗剂，没有已知的激动剂活性，用于治疗晚期乳腺癌。方法。患有晚期乳腺癌的绝经后妇女被随机分配接受单次 5 ml 肌内注射 250 mg 氟维司群，或两次 2.5 ml 肌内注射，总共 250 mg 氟维司群。注射后28天内采集血样进行药代动力学分析。结果。两种给药方法后 28 天均可测量氟维司群的血浆浓度。浓度-时间曲线相对较浅，从给药后 3 小时到第 28 天测量的 C-min 跨越了大约三倍的范围。氟维司群的血浆峰浓度 (C-max) 出现在给药后 1 至 11 天之间，一次 5-ml 注射和两次 2.5-ml 注射后平均 C-max 值分别为 6.0 和 6.2 ng/ml。两个给药组的血浆浓度-时间曲线在持续时间和浓度方面非常相似，并且氟维司群的总体暴露量相似（单次注射组与双次注射组的 AUC（0-28）之比为 1.01；95% 置信区间为 0.68-1.51）。结论。这项研究没有发现一次 5 毫升注射剂和两次 2.5 毫升注射剂之间存在任何药代动力学差异的证据。这两种方法可以互换使用，具体取决于哪种方法在任何特定的临床环境中更方便。
Purpose. To compare the pharmacokinetics of two different dosing methods of fulvestrant ('Faslodex'), an estrogen receptor antagonist with no known agonist activity, for the treatment of advanced breast cancer. Methods. Postmenopausal women with advanced breast cancer were randomly assigned to receive a single 5-ml intramuscular injection of 250 mg fulvestrant, or two 2.5-ml intramuscular injections with a total of 250 mg fulvestrant. Blood samples were taken for pharmacokinetic analysis up to 28 days after injection. Results. Plasma concentrations of fulvestrant were measurable up to 28 days after both dosing methods. The concentration-time profiles were relatively shallow, spanning an approximate threefold range from 3 h after dosing to C-min measured on day 28. Peak plasma concentrations (C-max) of fulvestrant occurred between 1 and 11 days after dosing, with mean C-max values of 6.0 and 6.2 ng/ml following one 5-ml injection and two 2.5-ml injections, respectively. The plasma concentration-time profiles were very similar in terms of duration and concentration, and overall exposure to fulvestrant was similar in both dosing groups (the ratio of the AUC(0-28) of the single-injection group to that of the double-injection group was 1.01; 95% confidence interval 0.68-1.51). Conclusion. This study found no evidence of any pharmacokinetic difference between one 5-ml injection and two 2.5-ml injections. The two methods can be used interchangeably, depending on which is more convenient in any particular clinical setting.