Tamoxifen and toremifene concentrations in plasma are greatly decreased by rifampin
Tamoxifen and toremifene concentrations in plasma are greatly decreased by rifampin
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DOI：
10.1016/s0009-9236(98)90055-8
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发表时间：
1998-12-01
影响因子：
6.7
通讯作者：
Neuvonen, PJ
中科院分区：
文献类型：
--
作者：
Kivistö, KT;Villikka, K;Neuvonen, PJ
利福平（INN，利福平）是参与药物代谢的细胞色素P450 （CYP）酶的有效诱导剂，因此引起许多药物相互作用。方法采用2项随机、安慰剂对照交叉研究，观察利福平对他莫昔芬（研究1）和托瑞米芬（研究2）药代动力学的影响。10名（研究1）或9名（研究2）健康男性志愿者。每日一次口服600毫克利福平或安慰剂，连续5天。第6天口服他莫昔芬80 mg或托瑞米芬120 mg。在给药后336小时采集血液样本。结果：利福平使他莫昔芬的血药-时间曲线下面积（AUC）降低86% (P < 0.001)，血药峰浓度（C-max）降低55% (P < 0.001)，消除半衰期（t(1/2)）降低44% （P < 0.001）。托瑞米芬的AUC降低了87% (P < 0.001)， C-max降低了55% (P < 0.001)， t /2降低了44% （P < 0.01）。在利福平期，n -去甲基他莫昔芬的AUC为38% (P < 0.001)， n -去甲基托瑞米芬的AUC为20% （P < 0.001）
Background Rifampin (INN, rifampicin) is a potent inducer of cytochrome P450 (CYP) enzymes involved in drug metabolism and therefore causes many drug interactions.Methods The effects of rifampin on the pharmacokinetics of tamoxifen (study I) and toremifene (study II) were examined in 2 randomized, placebo-controlled crossover studies. Ten (study I) or 9 (study II) healthy male volunteers took. either 600 mg rifampin or placebo orally once a day for 5 days. On the sixth day, 80 mg tamoxifen or 120 mg toremifene was administered orally. Blood samples were collected up to 336 hours after drug administration.Results: Rifampin reduced the area under the plasma concentration-time curve (AUC) of tamoxifen by 86% (P < .001), peak plasma concentration (C-max) by 55% (P < .001), and elimination half-life (t(1/2)) by 44% (P < .001). The AUC of toremifene was reduced by 87% (P < .001), C-max by 55% (P < .001), and t 1/2 by 44%, (P < .01) with rifampin. During the rifampin phase, the AUC of N-demethyltamoxifen was 38% (P < .001) and the AUC of N-demethyltoremifene was 20% (P