| In vivo: |
| J Pharm Sci. 2008 Oct;97(10):4546-56. | | Pharmacokinetics and bioavailability of the flavonoid 7,8-benzoflavone in rats.[Pubmed: 18257033 ] | 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.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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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