Pharmacokinetics and bioavailability of the flavonoid 7,8-benzoflavone in rats.
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| Abstract |
The flavonoid 7,8-benzoflavone was recently identified as one of the most potent inhibitors of breast cancer resistance protein (BCRP); however, little is known of the in vivo disposition of 7,8-benzoflavone. The objective of this study was to investigate the pharmacokinetics and bioavailability of 7,8-benzoflavone in rats. Three intravenous (5, 10, and 25 mg/kg) and three oral (12.5, 25, and 50 mg/kg) doses were administered to female Sprague-Dawley rats. Plasma samples were analyzed by high-performance liquid chromatography. Pharmacokinetic analysis was conducted by WinNonlin and ADAPT II. The dose-normalized plasma concentration versus time curves did not superimpose with each other, indicating the nonlinear pharmacokinetics of 7,8-benzoflavone. 7,8-benzoflavone exhibited a large volume of distribution (V(ss) approximately 1.5 L/kg) and rapid oral absorption (t(max) < 30 min). The bioavailability of 7,8-benzoflavone was low (0.61-13.2%) and dose-dependent. A pharmacokinetic model with dose-dependent bioavailability, linear absorption and nonlinear elimination best described the pharmacokinetic profiles of 7,8-benzoflavone. Using a 50 mg/kg oral dose of 7,8-benzoflavone, we could significantly increase the AUC for the BCRP substrate nitrofurantoin, demonstrating the potential for BCRP-mediated drug interactions.
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| Authors | Xiaodong Wang, Marilyn E Morris |
| Journal | Journal of pharmaceutical sciences (J Pharm Sci) Vol. 97 Issue 10 Pg. 4546-56 (Oct 2008) ISSN: 1520-6017 [Electronic] United States |
| PMID | 18257033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association |
| Chemical References |
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