흰쥐에서 아피제닌이 타목시펜의 생체이용률에 미치는 영향

• 영문명: Effects of Apigenin, a Flavonoid, on the Bioavailability of Tamoxifen in Rats
• 발행기관: 대한약학회
• 저자명: 김양우(Yang-Woo Kim) 최준식(Jun-Shik Choi)
• 간행물 정보: 『약학회지』제54권 제5호 (2010년), 370~376쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2010.10.31

영문 초록

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 (IC50) of 1.8 μM. 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 (Cmax) 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.

키워드

tamoxifen apigenin pharmacokinetics bioavailability rats