Pharmacokinetic properties of trifolirhizin, (-)-maackiain, (-)-sophoranone and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran after intravenous and oral administration of Sophora tonkinensis extract in rats.

Abstract

1. SKI3301, a standardized dried 50% ethanolic extracts of Sophora tonkinensis, contains four marker compounds (trifolirhizin, TF; (-)-maackiain, Maack; (-)-sophoranone, SPN, and (2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran, ABF), is being developed as an herbal medicine for the treatment of asthma in Korea. This study investigates the pharmacokinetic properties of SKI3301 extract in rats. 2. The dose-proportional AUCs suggest linear pharmacokinetics of TF, Maack, SPN and ABF in the SKI3301 extract intravenous dose range of 5-20 mg/kg. After the oral administration of 200-1000 mg/kg of the extract, TF and Maack exhibited non-linearity due to the saturation of gastrointestinal absorption. However, linear pharmacokinetics of SPN and ABF were observed. 3. The absorptions of TF, Maack, SPN and ABF in the extract were increased relative to those of the respective pure forms due to the increased solubility and/or the decreased metabolism by other components in the SKI3301 extract. 4. No accumulation was observed after multiple dosing, and the steady-state pharmacokinetics of TF, Maack, SPN and ABF were not significantly different from those after a single oral administration of the extract. 5. The pharmacokinetics of TF, SPN and ABF were not significantly different between male and female rats after oral administration of the extract, but a significant gender difference in the pharmacokinetics of Maack in rats was observed. 6. Our findings may help to comprehensively elucidate the pharmacokinetic characteristics of TF, Maack, SPN and ABF and provide useful information for the clinical application of SKI3301 extract.

• Authors: Soo Min Jang, Soo Hyeon Bae, Woong-Kee Choi, Jung Bae Park, Doyun Kim, Jee Sun Min, Hunseung Yoo, Minseok Kang, Keun Ho Ryu, Soo Kyung Bae
• Journal: Xenobiotica; the fate of foreign compounds in biological systems (Xenobiotica) Vol. 45 Issue 12 Pg. 1092-104 ( 2015) ISSN: 1366-5928 [Electronic] England
• PMID: 26068519 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(4'-hydroxybenzoyl)-5,6-methylenedioxy-benzofuran
• Benzofurans
• Flavonoids
• Glucosides
• Heterocyclic Compounds, 4 or More Rings
• Plant Extracts
• Pterocarpans
• sophoranone
• trifolirhizin
• inermin

Topics

• Administration, Intravenous
• Administration, Oral
• Animals
• Area Under Curve
• Benzofurans (pharmacokinetics)
• Dose-Response Relationship, Drug
• Female
• Flavonoids (pharmacokinetics)
• Glucosides (pharmacokinetics)
• Half-Life
• Heterocyclic Compounds, 4 or More Rings (pharmacokinetics)
• Intestinal Absorption
• Male
• Plant Extracts (chemistry, pharmacokinetics)
• Plant Roots (chemistry)
• Pterocarpans (pharmacokinetics)
• Rats
• Sex Characteristics
• Solubility
• Sophora (chemistry)