title: Pharmacokinetics of Active Components of Yokukansan, a Traditional Japanese Herbal Medicine after a Single Oral Administration to Healthy Japanese Volunteers: A Cross-Over, Randomized Study.
abstract: BACKGROUND
  Yokukansan (YKS) is a traditional Japanese herbal medicine called kampo medicine in Japan. Its extract comprises seven crude drugs: Atractylodis lanceae rhizoma, Poria, Cnidii rhizoma, Uncariae uncis cum ramulus, Angelicae radix, Bupleuri radix, and Glycyrrhizae radix. YKS is used to treat neurosis, insomnia, as well as behavioral and psychological symptoms of dementia.
  
  
  OBJECTIVE
  To confirm the exposure and pharmacokinetics of the active components of YKS in healthy volunteers.
  
  
  METHODS
  A randomized, open-label, 3-arm, 3-period, crossover trial was conducted on 21 healthy Japanese volunteers at the Kochi Medical University between May 2012 and November 2012.
  
  
  METHODS
  Single oral administration of YKS (2.5 g, 5.0 g, or 7.5 g/day) during each period.
  
  
  METHODS
  Plasma concentrations of three active compounds in YKS, namely 18β-glycyrrhetinic acid (GA), geissoschizine methyl ether (GM), and hirsuteine (HTE).
  
  
  RESULTS
  The mean maximum plasma concentrations (Cmax) of GM and HTE increased dose-dependently (ranges: 0.650-1.98 ng/mL and 0.138-0.450 ng/mL, respectively). The times to maximum plasma concentration after drug administration (tmax) were 0.500 h for GM and 0.975-1.00 h for HTE. The apparent elimination half-lives (t1/2) were 1.72-1.95 h for GM and 2.47-3.03 h for HTE. These data indicate the rapid absorption and elimination of GM and HTE. On the other hand, the Cmax, tmax, and t1/2 of GA were 57.7-108 ng/mL, 8.00-8.01 h, and 9.39-12.3 h, respectively.
  
  
  CONCLUSIONS
  We demonstrated that pharmacologically active components of YKS are detected in humans. Further, we determined the pharmacokinetics of GM, HTE, and GA. This information will be useful to elucidate the pharmacological effects of YKS.
  
  
  BACKGROUND
  Japan Pharmaceutical Information Center JAPIC CTI-121811.
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Munekage
authors.affiliation: Department of Surgical Oncology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Ichikawa
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Ian
authors.initials: I
authors.lastname: Fukudome
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Munekage
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takezaki
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Kampo Formulations Development Center, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Igarashi
authors.affiliation: Department of Elderly General Medicine, Tokyo Medical University, Tokyo, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanyu
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hanazaki
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000470:Alkaloids / Q000097:blood; D019540:Area Under Curve; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000097:blood; D064368:Healthy Volunteers; D006801:Humans; D026121:Indole Alkaloids / Q000097:blood; D007564:Japan; D008297:Male; D020835:Medicine, Kampo; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D055815:Young Adult
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; C524644:Yi-Gan San; C110832:geissoschizine methylether; C119129:18alpha-glycyrrhetinic acid; C063774:hirsuteine; D006034:Glycyrrhetinic Acid