title: Decreased absorption of midazolam in the stomach due to low pH induced by co-administration of Banha-sasim-tang.
abstract: OBJECTIVE
  Banha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb-drug interactions and may modify the clinical safety profile of therapeutic drugs.
  
  
  METHODS
  We investigated the potential herb-drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1ʹ-hydroxymidazolam (1ʹ-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg).
  
  
  RESULTS
  It was found that the AUC of MDZ and 1ʹ-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein.
  
  
  CONCLUSIONS
  The altered pharmacokinetics of midazolam caused by co-administration with BSTin vivocould be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.
authors: BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors: Jun Hyeon
authors: 0000-0003-2007-0076
authors: JH
authors: Jo
authors: BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors: Sun Joo
authors: 0000-0001-7679-0270
authors: SJ
authors: Kim
authors: BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors: Woong Shik
authors: 0000-0002-6475-7139
authors: WS
authors: Nam
authors: BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors: Eun Ji
authors: 0000-0003-1233-9530
authors: EJ
authors: Seung
authors: BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors: Sangkyu
authors: 0000-0001-5343-701X
authors: S
authors: Lee
keywords: Banha-sasim-tang; Herb-drug interaction; Midazolam; Pharmacokinetics