Metabolism and plasma pharmacokinetics of isoorientin, a natural active ingredient, in Sprague-Dawley male rats after oral and intravenous administration

Abstract

1. Several pharmacological effects have been revealed on isoorientin, suggesting its potential medicinal prospects. The metabolic and plasma pharmacokinetic profiles of isoorientin were investigated in rats.

2. For intra-gastric gavage, parent drug and three metabolites were detected in urine and feces by HPLC–MS/MS, but only one metabolite was found in plasma and identified as isoorientin 3′- or 4′-O-sulfate (M1) according to MS and UV absorbance spectra.

3. After a single i.v. administration of isoorientin (5, 10, or 15 mg/kg B.W.) in rats, linear pharmacokinetic property was observed with favorable terminal half-lives (1.67 ± 1.32–2.07 ± 0.50 h). After a single p.o. administration of isoorientin (150 mg/kg B.W.) in rats, plasma isoorientin concentration was low, but the concentration of M1 was comparatively high. Low systemic exposure of oral isoorientin in rats could result from its low aqueous solubility and extensive first-pass metabolism, and plasma concentration of M1 can be used as a biomarker of isoorientin intake. Isoorientin showed low oral bioavailability (8.98 ± 1.07%), and had about 6% or 45% dose recovery in urine or feces, respectively, 72 h after intra-gastric gavage.

4. These studies are the first to describe the pharmacokinetics of isoorientin via i.v. or p.o. dosing, providing important information for understanding its process in vivo.

• Isoorientin
• metabolism
• pharmacokinetics

Declaration of interest

The authors gratefully acknowledge the financial supports of the National Nature Science Foundation (No. 81303298 and 81202987) of China, and the Fujian Agriculture and Forestry University Foundation for excellent youth teachers (xjq201414). The authors declare no conflict of interest.

Supplementary material available online

Supplementary Figure S1-S4