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

摘要

Alpinia officinarumHance 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 andA.?officinarumbased 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 ofA.?officinarumand applied to comparative pharmacokinetic, tissue distribution and excretion studies. Our results clarified that oral administration ofA.?officinarumproduced significant alterations in the pharmacokinetic parameters of indomethacin. And the pharmacokinetic interaction between indomethacin andA.?officinarumreduced the systemic exposure of indomethacin and increased its elimination. Tissue distribution results demonstrated that co-administration ofA.?Officinarumcould 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.?Officinarummight have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.