Concurrent measurement of unbound genistein in the blood, brain and bile of anesthetized rats using microdialysis and its pharmacokinetic application

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Title:	Concurrent measurement of unbound genistein in the blood, brain and bile of anesthetized rats using microdialysis and its pharmacokinetic application
Authors:	Tsai, TH
Contributors:	中醫學院中醫所 Natl Res Inst Chinese Med, Taipei 112, Taiwan;China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan;Natl Yang Ming Univ, Inst Tradit Med, Taipei 112, Taiwan
Date:	2005
Issue Date:	2010-09-20 13:44:14 (UTC+8)
Publisher:	ELSEVIER SCIENCE BV
Abstract:	Genistein, the major isoflavone in soybeans, has been shown to have a wide range of effects. We used an HPLC-UV combined with microdialysis method to detect unbound genistein in rat blood, brain and bile. Genistein dialysates were eluted with a mobile phase containing acetonitrile-water (40:60, v/v, pH 3.5 adjusted by 0.1% acetic acid). Samples were separated using a phenyl (5 μ m) column maintained at ambient temperature. The UV detector wavelength was set at 259 nm. The flow rate was 1.0 ml/min. The limit of quantitation for genistein was 50 ng/ml. The in vitro recoveries of genistein were 31 &PLUSMN; 1, 13 &PLUSMN; 1 and 59 &PLUSMN; 4% in microdialysis probes of blood, brain and bile, respectively (n = 4). Inter- and intra-assay accuracy and precision of the analysis were less than 10% in the concentration ranges of 0.05-5.0 μ g/ml. A small ratio of genistein penetrates the blood-brain barrier (BBB) and goes through hepatobiliary excretion after genistein administration (10 or 30 mg/kg, i.v.). The brain-to-blood (AUC(brain)/AUC(blood)) and bile-to-blood (AUC(bile)/AUC(blood)) distribution ratios were 0.04 &PLUSMN; 0.01 and 1.85 &PLUSMN; 0.42, respectively for the dosage of genistein 30 mg/kg. After co-administration of cyclosporine, a P-glycoprotein (P-gp) inhibitor, the distribution ratios of genistein in brain and bile were not significantly altered. These results suggest that the BBB penetration and hepatobiliary excretion of genistein may not regulated by P-gp. &COPY; 2004 Elsevier B.V. All rights reserved.
Relation:	JOURNAL OF CHROMATOGRAPHY A 1073(1月2日):317-322
Appears in Collections:	[Graduate Institute of Chinese Medical Science] Proceedings

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