Environ Health Toxicol.  2016 ;31(1):e2016016. 10.5620/eht.e2016016.

Decreased absorption of midazolam in the stomach due to low pH induced by co-administration of Banha-sasim-tang

• Jo JH
• Kim SJ
• Nam WS
• Seung EJ
• Lee S

• KMID: 2469672
• DOI: http://doi.org/10.5620/eht.e2016016

Abstract

OBJECTIVES
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 1Í´-hydroxymidazolam (1Í´-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 1Í´-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 BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.

Keyword

Herb-drug interaction; Pharmacokinetics; Banha-sasim-tang; Midazolam

MeSH Terms

Absorption*
Administration, Oral
Animals
Area Under Curve
Cytochrome P-450 Enzyme System
Far East
Herb-Drug Interactions
Herbal Medicine
Hydrogen-Ion Concentration*
Mice
Midazolam*
Oral Mucosal Absorption
P-Glycoprotein
Pharmacokinetics
Plasma
Stomach*
Cytochrome P-450 Enzyme System
Midazolam
P-Glycoprotein