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

Autor:	Mijntje B. Vastbinder, Agnes Jager, Roelof W F van Leeuwen, Leonie J van Harten, Esther Oomen-de Hoop, Leontine E.A. Spierings, Ron H.J. Mathijssen, Teun van Gelder, Koen G A M Hussaarts, Stan Berghuis, Daan P. Hurkmans, Robbert J. van Alphen, Ron H.N. van Schaik, Quirine C. van Rossum-Schornagel
Přispěvatelé:	Medical Oncology, Clinical Chemistry, Pharmacy
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	Cancer Research Pharmacology lcsh:RC254-282 030226 pharmacology & pharmacy Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics SDG 3 - Good Health and Well-being medicine curcumin skin and connective tissue diseases Active metabolite CYP3A4 tamoxifen piperine Area under the curve drug interactions Prodrug lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Oncology chemistry 030220 oncology & carcinogenesis Piperine Curcumin pharmacokinetics Tamoxifen hormones hormone substitutes and hormone antagonists medicine.drug
Zdroj:	Cancers Volume 11 Issue 3 Cancers, 11(3):403. Multidisciplinary Digital Publishing Institute (MDPI) Cancers, Vol 11, Iss 3, p 403 (2019)
ISSN:	2072-6694
DOI:	10.3390/cancers11030403
Popis:	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&ndash 30mg per day (q.d.)) was either given alone, or combined with curcumin (1200 mg three times daily (t.i.d.)) +/&minus 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 AUC0&ndash 24h decreased with 7.7% (95%CI: &minus 15.4 to 0.7% p = 0.07) with curcumin and 12.4% (95%CI: &minus 21.9 to &minus 1.9% p = 0.02) with curcumin and piperine, compared to tamoxifen alone. Tamoxifen AUC0&ndash 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 (+/&minus piperine). Therefore, co-treatment with curcumin could lower endoxifen concentrations below the threshold for efficacy (potentially 20&ndash 40% of the patients), especially in EM patients.
Databáze:	OpenAIRE
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