Impact of Irradiation on the Pharmacokinetics and Biotransformation of Tamoxifen

被引：1

作者：

Cheng, Yung-Yi ^{[1
,2
]}

Zheng, Teresa ^{[1
]}

Chang, Michael W. ^{[1
]}

Dalley, Jeffrey W. ^{[3
,4
]}

Chen, Yu-Jen ^{[5
,6
,7
,8
]}

Tsai, Tung-Hu ^{[2
,3
]}

Hsieh, Chen-Hsi ^{[2
,9
,10
]}

机构：

[1] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacoengn & Mol Pharmaceut, Chapel Hill, NC 27599 USA

[2] Natl Yang Ming Chiao Tung Univ, Inst Tradit Med, Taipei, Taiwan

[3] Univ Cambridge, Dept Psychol, Cambridge, England

[4] Univ Cambridge, Dept Psychiat, Cambridge, England

[5] MacKay Mem Hosp, Dept Radiat Oncol, Taipei, Taiwan

[6] MacKay Jr Coll Med Nursing & Management, Dept Artificial Intelligence & Med Applict, Taipei, Taiwan

[7] China Med Univ Hosp, Dept Med Res, Taichung, Taiwan

[8] MacKay Mem Hosp, Dept Med Res, New Taipei, Taiwan

[9] Natl Yang Ming Chiao Tung Univ, Fac Med, Sch Med, Taipei, Taiwan

[10] Far Eastern Mem Hosp, Dept Radiol, Div Radiat Oncol, New Taipei, Taiwan

来源：

FRONTIERS IN ONCOLOGY | 2022年 / 12卷

关键词：

breast cancer; radiotherapy; tamoxifen; pharmacokinetics; tandem mass spectrometry; SURGICAL ADJUVANT BREAST; CANCER; RADIOTHERAPY; RECEPTOR; PREVENTION; FIBROSIS; WOMEN; ANTIESTROGEN; DEGRADATION; METABOLITE;

D O I：

10.3389/fonc.2022.833108

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundThe optimal procedure for combining radiotherapy (RT) with tamoxifen treatment is controversial as RT may alter the pharmacokinetics and biotransformation of tamoxifen. The present study investigated this potential interaction by assessing the pharmacokinetics of tamoxifen during concurrent and sequential RT. MethodPlasma tamoxifen concentration was measured in rats with or without RT 2.0 Gy (RT2.0Gy) or 0.5 Gy (RT0.5Gy) with ultra-high-performance liquid chromatography-tandem mass spectrometry after tamoxifen administration (10 mg/kg, p.o., n = 6). Tamoxifen was either administered 1 h after RT (concurrent condition) or 24 h after RT (sequential condition). ResultsPharmacokinetic data analysis demonstrated that the area under the curve (AUC) and half-life of tamoxifen were 2,004 +/- 241 h ng/ml and 6.23 +/- 1.21 h, respectively, after tamoxifen administration (10 mg/kg, p.o.). The respective conversion rate of 4-hydroxytamoxifen, N-desmethytamoxifen, and endoxifen for tamoxifen metabolism was 20%, 16%, and 5%. The AUC value of tamoxifen in the RT0.5Gy group was 1.5- to 1.7-fold higher than in the sham and RT2.0Gy groups. The relative bioavailability of tamoxifen at concurrent RT0.5Gy and RT2.0Gy groups ranged from 127% to 202% and from 71% to 152%, respectively. The magnitude of endoxifen, which converted from 4-hydroxytamoxifen and N-desmethyltamoxifen, increased 3- to 5-fold in the concurrent RT groups. By contrast, the AUC of tamoxifen decreased by roughly 24% in the sequential RT2.0Gy group. The conversion ratio of endoxifen was four times higher than that in the sequential RT2.0Gy group compared with rats not exposed to RT. ConclusionThe current study provides advanced pharmacokinetic data to confirm the interaction between RT and hormone therapy. Our findings indicate that RT facilitates the metabolism of tamoxifen to active metabolites and thus imply that combination RT-tamoxifen has potential benefits for the treatment of hormone-dependent breast cancer.

引用

页数：9

共 54 条

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