Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen

Tamoxifen, a widely prescribed medication in premenopausal women diagnosed with hormone-dependent breast cancer, is potentially co-prescribed with Hedyotis diffusa (H. diffusa), particularly in Taiwan. However, no related report has investigated the drug-herb interaction of H. diffusa on the pharmac...

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Autores principales:	Yung-Yi Cheng, Elise T. Tuzo, Jeffrey W. Dalley, Tung-Hu Tsai
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Tamoxifen Hedyotis diffusa 4-hydroxytamoxifen Endoxifen Herb-drug pharmacokinetic interaction UPLC-MS/MS Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6e520603c9484046a50077cffff07e98
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spelling	oai:doaj.org-article:6e520603c9484046a50077cffff07e982021-11-28T04:28:28ZDose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen0753-332210.1016/j.biopha.2021.112466https://doaj.org/article/6e520603c9484046a50077cffff07e982022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S075333222101252Xhttps://doaj.org/toc/0753-3322Tamoxifen, a widely prescribed medication in premenopausal women diagnosed with hormone-dependent breast cancer, is potentially co-prescribed with Hedyotis diffusa (H. diffusa), particularly in Taiwan. However, no related report has investigated the drug-herb interaction of H. diffusa on the pharmacokinetics of tamoxifen and its metabolites. In the present study, male Sprague-Dawley rats were administered different doses of H. diffusa extract for 5 consecutive days prior to the administration of tamoxifen (10 mg/kg). A validated ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) system was developed to monitor tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and endoxifen in rat plasma. Pharmacokinetic results demonstrated that the area under curves (AUCs) of tamoxifen and the relative bioavailability (%) of tamoxifen were dose-dependently decreased (31–68%) by pre-treatment with H. diffusa extract (3 g/kg and 6 g/kg). In addition, the conversion ratio of 4-hydroxytamoxifen was downregulated (0.5-fold change) and the N-desmethyltamoxifen conversion ratio was upregulated (2-fold change) by high-dose H. diffusa extract. As a result, the relative bioavailability and biotransformation changes affect the clinical efficacy of tamoxifen treatment. These preclinical findings reveal a hitherto unreported interaction between tamoxifen and H. diffusa extract that has implications for their therapeutic efficacy in treating breast cancer.Yung-Yi ChengElise T. TuzoJeffrey W. DalleyTung-Hu TsaiElsevierarticleTamoxifenHedyotis diffusa4-hydroxytamoxifenEndoxifenHerb-drug pharmacokinetic interactionUPLC-MS/MSTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112466- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tamoxifen Hedyotis diffusa 4-hydroxytamoxifen Endoxifen Herb-drug pharmacokinetic interaction UPLC-MS/MS Therapeutics. Pharmacology RM1-950
spellingShingle	Tamoxifen Hedyotis diffusa 4-hydroxytamoxifen Endoxifen Herb-drug pharmacokinetic interaction UPLC-MS/MS Therapeutics. Pharmacology RM1-950 Yung-Yi Cheng Elise T. Tuzo Jeffrey W. Dalley Tung-Hu Tsai Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen
description	Tamoxifen, a widely prescribed medication in premenopausal women diagnosed with hormone-dependent breast cancer, is potentially co-prescribed with Hedyotis diffusa (H. diffusa), particularly in Taiwan. However, no related report has investigated the drug-herb interaction of H. diffusa on the pharmacokinetics of tamoxifen and its metabolites. In the present study, male Sprague-Dawley rats were administered different doses of H. diffusa extract for 5 consecutive days prior to the administration of tamoxifen (10 mg/kg). A validated ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) system was developed to monitor tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and endoxifen in rat plasma. Pharmacokinetic results demonstrated that the area under curves (AUCs) of tamoxifen and the relative bioavailability (%) of tamoxifen were dose-dependently decreased (31–68%) by pre-treatment with H. diffusa extract (3 g/kg and 6 g/kg). In addition, the conversion ratio of 4-hydroxytamoxifen was downregulated (0.5-fold change) and the N-desmethyltamoxifen conversion ratio was upregulated (2-fold change) by high-dose H. diffusa extract. As a result, the relative bioavailability and biotransformation changes affect the clinical efficacy of tamoxifen treatment. These preclinical findings reveal a hitherto unreported interaction between tamoxifen and H. diffusa extract that has implications for their therapeutic efficacy in treating breast cancer.
format	article
author	Yung-Yi Cheng Elise T. Tuzo Jeffrey W. Dalley Tung-Hu Tsai
author_facet	Yung-Yi Cheng Elise T. Tuzo Jeffrey W. Dalley Tung-Hu Tsai
author_sort	Yung-Yi Cheng
title	Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen
title_short	Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen
title_full	Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen
title_fullStr	Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen
title_full_unstemmed	Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen
title_sort	dose-dependent effects of hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and n-desmethyltamoxifen
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/6e520603c9484046a50077cffff07e98
work_keys_str_mv	AT yungyicheng dosedependenteffectsofhedyotisdiffusaextractonthepharmacokineticsoftamoxifen4hydroxytamoxifenandndesmethyltamoxifen AT elisettuzo dosedependenteffectsofhedyotisdiffusaextractonthepharmacokineticsoftamoxifen4hydroxytamoxifenandndesmethyltamoxifen AT jeffreywdalley dosedependenteffectsofhedyotisdiffusaextractonthepharmacokineticsoftamoxifen4hydroxytamoxifenandndesmethyltamoxifen AT tunghutsai dosedependenteffectsofhedyotisdiffusaextractonthepharmacokineticsoftamoxifen4hydroxytamoxifenandndesmethyltamoxifen
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Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen

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