Clinical pharmacology of tamoxifen in patients with breast cancer: comparison of traditional and loading dose schedules.
Clinical pharmacology of tamoxifen in patients with breast cancer: comparison of traditional and loading dose schedules.
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发表时间：
1980-06
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通讯作者：
C. Fabian;L. Sternson;M. Barnett
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作者：
C. Fabian;L. Sternson;M. Barnett
转移性乳腺癌患者单剂量连续给药后，采用传统剂量方案10 mg/m~2，每日两次，单剂量20 mg/m~2，以及20~80 mg/m~2，每日两次×7天，然后20 mg/m~2单次每日剂量，测定转移性乳腺癌患者的血药浓度。使用传统的每日两次10 mg/m2的方案，连续给药后临床反应观察时的数值大于或等于单次给药后观察到的10倍峰值。使用每天两次×7天的负荷剂量计划大于或等于40 mg/m2×7天，已知与应答相关的值出现3小时，而不是传统计划大于或等于7天。根据每天一次的时间表，在高峰和低谷时间获得的水平表明，他莫昔芬可以安全地每天服用一次，特别是在治疗的前8周之后。持续给药后他莫昔芬的半衰期延长，停药后长达6周的水平表明，如果在延长他莫昔芬服药4-6周内对组织进行ER采样，则可能获得假阴性的细胞质雌激素受体(ER)检测。
Tamoxifen blood levels were measured in patients with metastatic breast cancer after single-dose and continuous administration, using a traditional dose schedule of 10 mg/m2 twice daily, a single daily dose schedule of 20 mg/m2; and several loading dose schedules of 20-80 mg/m2 twice daily x 7 days, then a 20-mg/m2 single daily dose thereafter. Using the traditional 10-mg/m2 twice daily schedule, values after continuous administration at the time clinical responses were observed were greater than or equal to 10 x peak values observed after a single dose. Using a loading dose schedule of greater than or equal to 40 mg/m2 twice daily x 7 days, values known to be associated with a response were present by 3 hours, as opposed to greater than or equal to 7 days with the traditional schedule. Levels obtained at peak and trough times with the once-daily schedule suggest tamoxifen may safely be given on a once-daily basis, particularly after the first 8 weeks of therapy. Half-life of tamoxifen after continuous administration is prolonged, and levels obtained for up to 6 weeks after drug discontinuation suggest that false-negative cytoplasmic estrogen receptor (ER) determinations may be obtained if tissue for ER is sampled within 4-6 weeks of prolonged tamoxifen administration.