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dc.contributor.authorCheng, Yung-Yi
dc.contributor.authorZheng, Teresa
dc.contributor.authorChang, Michael W
dc.contributor.authorDalley, Jeffrey W
dc.contributor.authorChen, Yu-Jen
dc.contributor.authorTsai, Tung-Hu
dc.contributor.authorHsieh, Chen-Hsi
dc.date.accessioned2022-03-03T09:00:13Z
dc.date.available2022-03-03T09:00:13Z
dc.date.issued2022
dc.date.submitted2021-12-10
dc.identifier.issn2234-943X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334621
dc.description.abstractBACKGROUND: The 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. METHOD: Plasma 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). RESULTS: Pharmacokinetic 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. CONCLUSION: The 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.
dc.languageen
dc.publisherFrontiers Media SA
dc.subjectOncology
dc.subjectbreast cancer
dc.subjectradiotherapy
dc.subjecttamoxifen
dc.subjectpharmacokinetics
dc.subjecttandem mass spectrometry
dc.titleImpact of Irradiation on the Pharmacokinetics and Biotransformation of Tamoxifen.
dc.typeArticle
dc.date.updated2022-03-03T09:00:13Z
prism.publicationNameFront Oncol
prism.volume12
dc.identifier.doi10.17863/CAM.82040
dcterms.dateAccepted2022-01-24
rioxxterms.versionofrecord10.3389/fonc.2022.833108
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidDalley, Jeffrey [0000-0002-2282-3660]
dc.identifier.eissn2234-943X
cam.issuedOnline2022-02-17


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