title: Pharmacokinetic Profiles of Active Components After Oral Administration of a Kampo Medicine, Shakuyakukanzoto, to Healthy Adult Japanese Volunteers.
abstract: Shakuyakukanzoto (SKT), a traditional Japanese (Kampo) medicine, has been used by patients with muscle cramps and abdominal pains. In this trial, we analyzed plasma concentrations of active components after SKT was administered as a single oral dose of 2.5 or 5.0 g/day per person. The study was a randomized, open-label, two-arm, two-period, crossover trial conducted in healthy Japanese volunteers. Albiflorin (ALB), paeoniflorin (PAE), glycycoumarin (GCM), isoliquiritigenin (ILG), glycyrrhetic acid (GA), and glycyrrhetic acid-3-O-monoglucuronide were targeted, and the plasma concentration of each component was measured using a liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were calculated, and the linearity was assessed. All targeted components were detected in the plasma after oral administration of SKT. ALB, PAE, GCM, and ILG were detected at an early stage. The linearity was observed for the maximum plasma concentration of GCM, ILG, and GA and for the area under the plasma concentration-time curve of GA. In this trial, we demonstrated for the first time in humans that these components were absorbed into the blood after oral administration of SKT. The results of this pharmacokinetic trial in humans are also important and useful for understanding the mechanism of action of SKT, verifying the active components predicted in basic research, and conducting pharmacokinetics and safety studies in the future.
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Sadakane
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan. Electronic address: watanabe_junko@mail.tsumura.co.jp.
authors.forename: Junko
authors.initials: J
authors.lastname: Watanabe
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Fukutake
authors.affiliation: Kampo Formulations Development Center, Production Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nisimura
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Maemura
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy; D000284:Administration, Oral; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006035:Glycyrrhiza; D006801:Humans; D020835:Medicine, Kampo; D008875:Middle Aged; D009120:Muscle Cramp / Q000188:drug therapy; D029596:Paeonia; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D000700:Analgesics; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; C038462:shakuyaku-kanzoh-toh
keywords: Clinical pahrmacokinetics; Dose-response; Intestinal absorption; Intestinal metabolism; Mebabolite kinetics; Shakuyaku-kanzo-to; TJ-68; healthy adult volunteers; randomized crossover study