Does Rabeprazole Sodium Alleviate the Anti-diabetic Activity of Linagliptin? Drug-Drug Interaction Analysis by In vitro and In vivo Methods

Abstract

Drug interaction has turned into the preeminent regarding issues for a prescriber during polypharmacy. The foremost objective of this research was to form a complex between linagliptin and rabeprazole sodium by in vitro interactions. The interactions between the drugs have been examined by monitoring some chromatographic and spectroscopic analyses viz. TLC, HPLC, FT-IR, UV, Job’s plot, conductometric titrations, and Ardon’s spectrophotometric strategy. Rabeprazole sodium formed a stable complex with linagliptin, which was ensured from the insight of these analytical data. The developed complex’s bright spot was clearly watched in the TLC plate. The retention time (Rt) of the formed complex was 5.303 min, where the Rt were 3.364 and 3.103 min for linagliptin and rabeprazole sodium, respectively, in HPLC chromatograms. In FT-IR and UV spectra of the formed complex revealed some disappearance of characteristic peaks that affirmed the complexation. All of the variations of the spectrophotometric and chromatographic properties from the antecedent drugs indicated the drug-drug interaction. Another crucial fact for the experimental aim was to affirm the assumed drug interaction by in vivo model examination. The assessment of anti-diabetic property on alloxan-induced Swiss albino mice proved significant in vivo interaction between the drugs. It was outlined from the animal study that the hypoglycemic activity of linagliptin might be significantly affected due to the complex formation of the drug with a proton pump inhibitor (PPI). Nonetheless, it is the primary outcome of the interaction, which recommends the bigger in vivo study or clinical monitoring on the human model.

Interactions of linagliptin, rabeprazole sodium, and their formed complex with bovine serum albumin: Computational docking and fluorescence spectroscopic methods

“…The lower protein binding affinity of the formed complex may construe lower potency and significantly lower the hypoglycemic effect of LG. This hypothetical interpretation of the fluorescence spectroscopic study was validated through in vivo research conducted by Hossain et al13…”

“…About 90% of the drug is excreted in the urine, basically as thioether carboxylic acid, as well as its metabolites of glucuronide and mercapturic acid 12 . As LG prescribed diabetic patients may take RS, the thermodynamic study of the developed complex between the two drugs is essential to interpret the plausible drug–drug interaction 13 …”

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

“…Drug resistance is the major drawback of the antiviral, antifungal, antibacterial, antimalarial, anti-cancer, anti-hepatitis, and anti-HIV agents ( Wang et al, 2015 ). Another notable concern is that several benzimidazole derivatives such as PPIs are showing in vitro and in vivo drug-drug interactions with several classes of therapeutics such as anti-cancer ( Bezabeh et al, 2012 ) and antidiabetics ( Hossain et al, 2020 ; Hossain et al, 2021 ).…”

Transition Metal Chelation Augments the Half-life of Secnidazole: Molecular Docking and Fluorescence Spectroscopic Approaches

“…The corresponding Stern-Volmer quenching constants (Ksv), and quenching rate constants (k q ) augmented with increasing temperature at physiological pH 7.4. This phosphate buffer was prepared by mixing of 65 mL of 0.01M KH 2 PO 4 with 235 mL of 0.01M K 2 HPO 4 and diluted to 1000 ml with DM water [34].…”