Herb-drug interaction in the protective effect of Alpinia officinarum against gastric injury induced by indomethacin based on pharmacokinetic, tissue distribution and excretion studies in rats

• Published in: Journal of pharmaceutical analysis 2021-04, Vol.11 (2), p.200-209
• Main Authors: Zhang, Xuguang, Xie, Zhenrui, Chen, Xun, Qiu, Junqiang, Tan, Yinfeng, Li, Xiaoliang, Li, Hailong, Zhang, Junqing
• Format: Article
• Language: English
• Subjects: Alpinia officinarum; Alpinia officinarum Hance; Diarrhea; Drug interaction; Drug interactions; Ethanol; Excretion; Feces; Herb-drug interaction; Herbs; Indomethacin; Laboratory animals; Mass spectrometry; Mass spectroscopy; Metabolites; Oral administration; Original; Pain; Pharmacokinetics; Plasma; Scientific imaging; Tissue distribution; Vomiting
• ISSN: 2095-1779; 2214-0883
• DOI: 10.1016/j.jpha.2020.05.009

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis, abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects. However, the role of herb-drug interaction between indomethacin and A. officinarum based on pharmacokinetic, tissue distribution and excretion still remains unknown. In this study, an ultra-fast liquid-tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous determination of indomethacin and its three metabolites, O-desmethylindomethacin (ODI), deschlorobenzoylindomethacin (NDI) and indomethacin acyl-β-D-glucuronide (IDAβG) by oral administration of indomethacin solution with and without the ethanolic extract of A. officinarum and applied to comparative pharmacokinetic, tissue distribution and excretion studies. Our results clarified that oral administration of A. officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin. And the pharmacokinetic interaction between indomethacin and A. officinarum reduced the systemic exposure of indomethacin and increased its elimination. Tissue distribution results demonstrated that co-administration of A. Officinarum could not reduce the accumulation of indomethacin in the target tissue of the stomach, but could accelerate the excretions of indomethacin and its three metabolites including ODI, NDI and IDAβG in the bile and feces of rats in the excretion study. Therefore, A. Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats. [Display omitted] •An UFLC-MS/MS method was developed for simultaneous determination of indomethacin and its metabolites by oral administration of indomethacin with and without A. officinarum Hance and applied to comparative pharmacokinetic, tissue distribution and excretion studies.•Our results first clarified that oral administration of A. officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin. And the pharmacokinetic interaction between indomethacin and A. officinarum leaded to reduce the systemic exposure of indomethacin and increase its elimination.•A. Officinarum could accelerate the excretions of indomethacin and its three metabolites in the bile and feces of rats in the excretion study. Therefore, A. Officinarum might be of the gastrointestinal protective effect through the i