COMEDICATION OF RABEPRAZOLE SODIUM CAUSES POTENTIAL DRUG-DRUG INTERACTION WITH DIABETIC DRUG LINAGLIPTIN: In-vitro AND In-silico APPROACHES

Abstract

Drug-drug interaction is a notable concern among physicians when prescribing multi-therapy to the patients as concomitant administration of multi-drugs might cause unexpected adverse drug reactions. The main objective of this research is to predict a potential drug-drug interaction between two frequently used drugs by diabetic patients, an antidiabetic drug (linagliptin) and a proton pump inhibitor (rabeprazole sodium). Here, several in vitro techniques, including thermal (melting point, thermogravimetric analysis [TGA]), morphological (scanning electron microscopy [SEM] and X-ray powder diffraction [XRPD] analysis), highly sophisticated synchronous fluorescence, and in silico methods were applied to anticipate the potential drug-drug interaction between these stated drugs quickly. The melting point and TGA study revealed thermochemical properties, thermal stability profiles, and degradation patterns upon temperature rising of the formed complex and these precursor drugs. The SEM and XRPD have provided the morphological changes like particle shape and size distribution of the desired molecule that might be caused due to the potential drug-drug interactions. Besides, the drastic reduction of the quenching rate constant of linagliptin during interaction with bovine serum albumin in synchronous fluorescence also endorsed the potential drug-drug interaction. Furthermore, the drug-receptor docking analysis demonstrated that the binding affinity of the precursor ligands might be reduced due to the predicted drug-drug interaction. However, the current evidence warrants extensive investigation to confirm the above-stated potential drug-drug interaction in the larger animal model. Finally, clinical data need to be closely monitored during the treatment of diabetic patients prescribed with linagliptin and rabeprazole sodium.