title: 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.affiliation: a College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea , Bucheon , Republic of Korea .
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Jang
authors.affiliation: b Department of Pharmacology , College of Medicine, The Catholic University of Korea , Seoul , Republic of Korea .
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Bae
authors.affiliation: a College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea , Bucheon , Republic of Korea .
authors.forename: Woong-Kee
authors.initials: WK
authors.lastname: Choi
authors.affiliation: a College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea , Bucheon , Republic of Korea .
authors.forename: Jung Bae
authors.initials: JB
authors.lastname: Park
authors.affiliation: a College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea , Bucheon , Republic of Korea .
authors.forename: Doyun
authors.initials: D
authors.lastname: Kim
authors.affiliation: a College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea , Bucheon , Republic of Korea .
authors.forename: Jee Sun
authors.initials: JS
authors.lastname: Min
authors.affiliation: c College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , Seoul , Republic of Korea .|d New Drug Preclinical & Analytical Team , and.
authors.forename: Hunseung
authors.initials: H
authors.lastname: Yoo
authors.affiliation: d New Drug Preclinical & Analytical Team , and.
authors.forename: Minseok
authors.initials: M
authors.lastname: Kang
authors.affiliation: e New Drug Team 1, Life Science R&D Center, SK Chemicals , Sungnam , Republic of Korea.
authors.forename: Keun Ho
authors.initials: KH
authors.lastname: Ryu
authors.affiliation: a College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea , Bucheon , Republic of Korea .
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Bae
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001572:Benzofurans / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000493:pharmacokinetics*; D005960:Glucosides / Q000493:pharmacokinetics*; D006207:Half-Life; D006576:Heterocyclic Compounds, 4 or More Rings / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics*; D018517:Plant Roots / Q000737:chemistry; D036343:Pterocarpans / Q000493:pharmacokinetics*; D051381:Rats; D012727:Sex Characteristics; D012995:Solubility; D029909:Sophora / Q000737:chemistry*; D000094162:Phytoalexins
chemical_list: D001572:Benzofurans; D005419:Flavonoids; D005960:Glucosides; D006576:Heterocyclic Compounds, 4 or More Rings; D010936:Plant Extracts; D036343:Pterocarpans; C560462:2-(4'-hydroxybenzoyl)-5,6-methylenedioxy-benzofuran; C461819:sophoranone; C526230:trifolirhizin; C001449:inermin; D000094162:Phytoalexins
keywords: (–)-maackiain; (–)-sophoranone; 2-(2,4-dihydroxyphenyl)-5; 6-methylenedioxybenzofuran; Pharmacokinetics; SKI3301; Sophora tonkinensis; rats; trifolirhizin