Effects of myricetin, an anticancer compound, on the bioavailability and pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats
- PMID: 21442417
- DOI: 10.1007/s13318-011-0036-y
Effects of myricetin, an anticancer compound, on the bioavailability and pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats
Abstract
This study examined the effect of myricetin, an anticancer compound, on the bioavailability and pharmacokinetics of tamoxifen and its metabolite, 4-hydroxytamoxifen, in rats. The effect of myricetin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 and 2C9 activity was evaluated. Myricetin inhibited CYP3A4 and 2C9 activity with IC(50) values of 7.81 and 13.5 μM, respectively, and significantly inhibited P-gp activity in a concentration-dependent manner. Pharmacokinetic parameters of tamoxifen and 4-hydroxytamoxifen were determined in rats after oral (10 mg/kg) and intravenous (2 mg/kg) administration of tamoxifen in the presence and absence of myricetin (0.4, 2, and 8 mg/kg). Compared with the oral control group (given tamoxifen alone), the area under the plasma concentration-time curve (AUC(0-∞)) and the peak plasma concentration (C (max)) of tamoxifen were significantly (P < 0.05, 2 mg/kg; P < 0.01, 8 mg/kg) increased by 41.8-74.4 and 48.4-81.7%, respectively. Consequently, the absolute bioavailability (AB) of tamoxifen with myricetin (2 and 8 mg/kg) was 29.0-35.7%, which was significantly enhanced (P < 0.05 for 2 mg/kg, P < 0.01 for 8 mg/kg) compared with the oral control group (20.4%). Moreover, the relative bioavailability (RB) of tamoxifen was 1.14- to 1.74-fold greater than that of the control group. The metabolite-parent AUC ratio (MR) was significantly reduced (P < 0.05, 8 mg/kg), implying that the formation of 4-hydroxytamoxifen was considerably affected by myricetin. The enhanced bioavailability of tamoxifen might be mainly due to inhibition of the CYP3A4- and CYP2C9-mediated metabolism of tamoxifen in the small intestine and/or in the liver, and inhibition of P-gp efflux pump in the small intestine by myricetin.
Similar articles
-
Effects of curcumin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen, in rats: possible role of CYP3A4 and P-glycoprotein inhibition by curcumin.Pharmazie. 2012 Feb;67(2):124-30. Pharmazie. 2012. PMID: 22512082
-
Effects of baicalein on the pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats: possible role of cytochrome P450 3A4 and P-glycoprotein inhibition by baicalein.Arch Pharm Res. 2011 Nov;34(11):1965-72. doi: 10.1007/s12272-011-1117-9. Epub 2011 Dec 3. Arch Pharm Res. 2011. PMID: 22139696
-
Effects of myricetin, an antioxidant, on the pharmacokinetics of losartan and its active metabolite, EXP-3174, in rats: possible role of cytochrome P450 3A4, cytochrome P450 2C9 and P-glycoprotein inhibition by myricetin.J Pharm Pharmacol. 2010 Jul;62(7):908-14. doi: 10.1211/jpp.62.07.0012. J Pharm Pharmacol. 2010. PMID: 20636879
-
Effects of silybinin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen in rats.Anticancer Res. 2010 Jan;30(1):79-85. Anticancer Res. 2010. PMID: 20150620
-
Enhanced bioavailability of tamoxifen after oral administration of tamoxifen with quercetin in rats.Int J Pharm. 2006 Apr 26;313(1-2):144-9. doi: 10.1016/j.ijpharm.2006.01.028. Epub 2006 Mar 3. Int J Pharm. 2006. PMID: 16516418
Cited by
-
Chemogenetic inhibition of subicular seizure-activated neurons alleviates cognitive deficit in male mouse epilepsy model.Acta Pharmacol Sin. 2023 Dec;44(12):2376-2387. doi: 10.1038/s41401-023-01129-z. Epub 2023 Jul 25. Acta Pharmacol Sin. 2023. PMID: 37488426
-
Phytochemicals That Interfere With Drug Metabolism and Transport, Modifying Plasma Concentration in Humans and Animals.Dose Response. 2022 Sep 21;20(3):15593258221120485. doi: 10.1177/15593258221120485. eCollection 2022 Jul-Sep. Dose Response. 2022. PMID: 36158743 Free PMC article. Review.
-
Interactions Between Natural Products and Tamoxifen in Breast Cancer: A Comprehensive Literature Review.Front Pharmacol. 2022 Jun 2;13:847113. doi: 10.3389/fphar.2022.847113. eCollection 2022. Front Pharmacol. 2022. PMID: 35721162 Free PMC article. Review.
-
Biotechnological Applications and Health-Promoting Properties of Flavonols: An Updated View.Int J Mol Sci. 2022 Feb 1;23(3):1710. doi: 10.3390/ijms23031710. Int J Mol Sci. 2022. PMID: 35163632 Free PMC article. Review.
-
Myricetin: A comprehensive review on its biological potentials.Food Sci Nutr. 2021 Aug 11;9(10):5854-5868. doi: 10.1002/fsn3.2513. eCollection 2021 Oct. Food Sci Nutr. 2021. PMID: 34646551 Free PMC article. Review.
References
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous