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The aim of this study is to investigate the effect of apigenin on the pharmacokinetics of tamoxifen in rats. Tamoxifen was administered orally (10 mg/kg) or intravenously (2 mg/kg) without or with oral administration of apigenin (0.4, 2.0 or 8.0 mg/kg) to rats. The effect of apigenin on the P-glycoprotein (P-gp) and CYP3A4 activity was also evaluated. Apigenin inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly enhanced the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. The plasma concentrations of tamoxifen were increased significantly by apigenin compared to control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations ($IC_{max}$) of tamoxifen with apigenin were significantly higher than those of the control group. Consequently, the relative bioavailability (RB%) of tamoxifen with apigenin was 2-3-fold higher than the control, and absolute bioavailability (AB%) of tamoxifen were significantly higher (p<0.05 with co-administration, p<0.01 with pretreatment) than those of the control. The increased bioavailability of tamoxifen in rats with apigenin might be associated with the inhibition of an efflux pump P-glycoprotein and CYP3A4 by apigenin. From these results, dosage regimen of tamoxifen may be need to adjust when concomitantly administered with apigenin.
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참고문헌 (40)
참고문헌 신청
Dixon, R. A / 1999 / Flavonoids and isoflavonoids -a gold mine for metabolic engineering / Trends Plant Sci 4:394
Galati, G / 2001 / Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation / Free Radical Biology & Medicine 30:370
Chuang, C. M / 2009 / Combination of apigenin treatment with therapeutic HPV DNA vaccination generates enhanced therapeutic antitumor effects / J. Biomed. Sci 16:49
Jeong, G. S / 2009 / Anti-inflammatory effects of apigenin on nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1 / Int. Immunopharmacol 9:1374
Gates, M. A / 2009 / Flavonoid intake and ovarian cancer risk in a population-based case-control study / Int. J. Cancer 124:1918
Galati, G / 2001 / Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation / Free Radical Biology & Medicine 30:370
Chuang, C. M / 2009 / Combination of apigenin treatment with therapeutic HPV DNA vaccination generates enhanced therapeutic antitumor effects / J. Biomed. Sci 16:49
Jeong, G. S / 2009 / Anti-inflammatory effects of apigenin on nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1 / Int. Immunopharmacol 9:1374
Gates, M. A / 2009 / Flavonoid intake and ovarian cancer risk in a population-based case-control study / Int. J. Cancer 124:1918
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