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Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen

Tamoxifen is a prodrug that is primarily metabolized into the pharmacologically active metabolite endoxifen and eventually into inactive metabolites. The herb curcumin may increase endoxifen exposure by affecting phase II metabolism. We compared endoxifen and tamoxifen exposure in breast cancer pati...

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Autores principales: Hussaarts, Koen G.A.M., Hurkmans, Daan P., Oomen-de Hoop, Esther, van Harten, Leonie J., Berghuis, Stan, van Alphen, Robbert J., Spierings, Leontine E.A., van Rossum-Schornagel, Quirine C., Vastbinder, Mijntje B., van Schaik, Ron H.N., van Gelder, Teun, Jager, Agnes, van Leeuwen, Roelof W.F., Mathijssen, Ron H.J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468355/
https://www.ncbi.nlm.nih.gov/pubmed/30909366
http://dx.doi.org/10.3390/cancers11030403
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author Hussaarts, Koen G.A.M.
Hurkmans, Daan P.
Oomen-de Hoop, Esther
van Harten, Leonie J.
Berghuis, Stan
van Alphen, Robbert J.
Spierings, Leontine E.A.
van Rossum-Schornagel, Quirine C.
Vastbinder, Mijntje B.
van Schaik, Ron H.N.
van Gelder, Teun
Jager, Agnes
van Leeuwen, Roelof W.F.
Mathijssen, Ron H.J.
author_facet Hussaarts, Koen G.A.M.
Hurkmans, Daan P.
Oomen-de Hoop, Esther
van Harten, Leonie J.
Berghuis, Stan
van Alphen, Robbert J.
Spierings, Leontine E.A.
van Rossum-Schornagel, Quirine C.
Vastbinder, Mijntje B.
van Schaik, Ron H.N.
van Gelder, Teun
Jager, Agnes
van Leeuwen, Roelof W.F.
Mathijssen, Ron H.J.
author_sort Hussaarts, Koen G.A.M.
collection PubMed
description Tamoxifen is a prodrug that is primarily metabolized into the pharmacologically active metabolite endoxifen and eventually into inactive metabolites. The herb curcumin may increase endoxifen exposure by affecting phase II metabolism. We compared endoxifen and tamoxifen exposure in breast cancer patients with or without curcumin, and with addition of the bio-enhancer piperine. Tamoxifen (20–30mg per day (q.d.)) was either given alone, or combined with curcumin (1200 mg three times daily (t.i.d.)) +/− piperine (10 mg t.i.d.). The primary endpoint of this study was the difference in geometric means for the area under the curve (AUC) of endoxifen. Genotyping was performed to determine CYP2D6 and CYP3A4 phenotypes. The endoxifen AUC(0–24h) decreased with 7.7% (95%CI: −15.4 to 0.7%; p = 0.07) with curcumin and 12.4% (95%CI: −21.9 to −1.9%; p = 0.02) with curcumin and piperine, compared to tamoxifen alone. Tamoxifen AUC(0–24h) showed similar results. For patients with an extensive CYP2D6 metabolism phenotype (EM), effects were more pronounced than for intermediate CYP2D6 metabolizers (IMs). In conclusion, the exposure to tamoxifen and endoxifen was significantly decreased by concomitant use of curcumin (+/− piperine). Therefore, co-treatment with curcumin could lower endoxifen concentrations below the threshold for efficacy (potentially 20–40% of the patients), especially in EM patients.
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spelling pubmed-64683552019-04-24 Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen Hussaarts, Koen G.A.M. Hurkmans, Daan P. Oomen-de Hoop, Esther van Harten, Leonie J. Berghuis, Stan van Alphen, Robbert J. Spierings, Leontine E.A. van Rossum-Schornagel, Quirine C. Vastbinder, Mijntje B. van Schaik, Ron H.N. van Gelder, Teun Jager, Agnes van Leeuwen, Roelof W.F. Mathijssen, Ron H.J. Cancers (Basel) Article Tamoxifen is a prodrug that is primarily metabolized into the pharmacologically active metabolite endoxifen and eventually into inactive metabolites. The herb curcumin may increase endoxifen exposure by affecting phase II metabolism. We compared endoxifen and tamoxifen exposure in breast cancer patients with or without curcumin, and with addition of the bio-enhancer piperine. Tamoxifen (20–30mg per day (q.d.)) was either given alone, or combined with curcumin (1200 mg three times daily (t.i.d.)) +/− piperine (10 mg t.i.d.). The primary endpoint of this study was the difference in geometric means for the area under the curve (AUC) of endoxifen. Genotyping was performed to determine CYP2D6 and CYP3A4 phenotypes. The endoxifen AUC(0–24h) decreased with 7.7% (95%CI: −15.4 to 0.7%; p = 0.07) with curcumin and 12.4% (95%CI: −21.9 to −1.9%; p = 0.02) with curcumin and piperine, compared to tamoxifen alone. Tamoxifen AUC(0–24h) showed similar results. For patients with an extensive CYP2D6 metabolism phenotype (EM), effects were more pronounced than for intermediate CYP2D6 metabolizers (IMs). In conclusion, the exposure to tamoxifen and endoxifen was significantly decreased by concomitant use of curcumin (+/− piperine). Therefore, co-treatment with curcumin could lower endoxifen concentrations below the threshold for efficacy (potentially 20–40% of the patients), especially in EM patients. MDPI 2019-03-22 /pmc/articles/PMC6468355/ /pubmed/30909366 http://dx.doi.org/10.3390/cancers11030403 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hussaarts, Koen G.A.M.
Hurkmans, Daan P.
Oomen-de Hoop, Esther
van Harten, Leonie J.
Berghuis, Stan
van Alphen, Robbert J.
Spierings, Leontine E.A.
van Rossum-Schornagel, Quirine C.
Vastbinder, Mijntje B.
van Schaik, Ron H.N.
van Gelder, Teun
Jager, Agnes
van Leeuwen, Roelof W.F.
Mathijssen, Ron H.J.
Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen
title Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen
title_full Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen
title_fullStr Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen
title_full_unstemmed Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen
title_short Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen
title_sort impact of curcumin (with or without piperine) on the pharmacokinetics of tamoxifen
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468355/
https://www.ncbi.nlm.nih.gov/pubmed/30909366
http://dx.doi.org/10.3390/cancers11030403
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