title: Pharmacokinetic Interaction Study of Ranitidine and Daijokito in Healthy Volunteers.
abstract: BACKGROUND
  Ranitidine is a histamine 2 receptor antagonist, and daijokito is a Kampo (Chinese herbal medicine as practiced in Japan) formula, which is traditionally used for treating constipation and digestive trouble. Previous study demonstrated that daijokito significantly affected the pharmacokinetics of ranitidine in rats; however, the doses of ranitidine and daijokito in that study were higher than in clinical practice. Therefore, we examined the pharmacokinetic interaction between ranitidine and daijokito in clinical practice doses in healthy volunteers.
  
  
  METHODS
  This was a randomized, open label, two-period crossover study in healthy volunteers (n = 7). Volunteers received administrations of either a single dose of ranitidine 300 mg, or ranitidine 300 mg in combination with daijokito extract granules 2.5 g. Plasma concentrations of ranitidine were measured over 12 h by LC/MS/MS method.
  
  
  RESULTS
  Plasma concentrations of ranitidine were lower with co-administration of daijokito compared with ranitidine alone. Co-administration of daijokito significantly decreased ranitidine area under the plasma concentration-time curve from 0 to 12 h (AUC0-12) and maximum plasma concentration (Cmax) with geometric mean (GM) ratio [90% confidence interval (CI)] for AUC0-12 of 0.609 (0.449, 0.826) and Cmax of 0.515 (0.345, 0.771).
  
  
  CONCLUSIONS
  Co-administration of ranitidine with daijokito resulted in a significant decrease in plasma level of ranitidine in healthy volunteers.
authors: Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors: Yusuke
authors: Y
authors: Endo
authors: Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors: Yoshitaka
authors: Y
authors: Ishihara
authors: Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors: Satoshi
authors: S
authors: Tsuno
authors: †Department of Fundamental Nursing, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors: Akiko
authors: A
authors: Matsuda
authors: Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors: Weibin
authors: W
authors: Qian
authors: Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors: Norimasa
authors: N
authors: Miura
authors: Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors: Junichi
authors: J
authors: Hasegawa
keywords: daijokito; drug-drug interaction; pharmacokinetics; ranitidine