Pharmacokinetics and bioavailability of the flavonoid 7,8-benzoflavone in rats

J Pharm Sci. 2008 Oct;97(10):4546-56. doi: 10.1002/jps.21296.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Benzoflavones / administration & dosage
  • Benzoflavones / blood
  • Benzoflavones / pharmacokinetics*
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Female
  • Infusions, Intravenous
  • Rats
  • Rats, Sprague-Dawley


  • Benzoflavones
  • alpha-naphthoflavone