title: Pharmacokinetics and bioavailability of the flavonoid 7,8-benzoflavone in rats.
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.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 517 Hochstetter Hall, Amherst, New York 14260, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Morris
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001571:Benzoflavones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D007262:Infusions, Intravenous; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001571:Benzoflavones; C011512:alpha-naphthoflavone