Analysis between Linagliptin and Azithromycin: In vitro and In vivo Interaction Study

Background: Linagliptin is prescribed as a dipeptidyl peptidase-4 (DPP-4) inhibitor. Azithromycin is specified as an antibiotic that binds with 23s rRNA of the 50s ribosomal subunit, obstructing the microbial protein synthesis. Our study focuses on the drug-drug interactions of these drugs. Objective: The purpose of the study is to understand the bioavailability and physicochemical approaches of Linagliptin and Azithromycin interaction mediated through the strength and nature of the complexation. Methods: The in vitro assessment of drug interaction was conducted using Ultraviolet-visible spectroscopy (UV/VIS), Ultra-Performance Liquid Chromatography (UPLC), Fourier transform infrared spectroscopy (FT-IR), and Differential scanning calorimetry (DSC), while the Oral Glucose Tolerance Test (OGTT) was performed for the in vivo assessment of drug interaction in a mouse model. Results: Mild variation in interaction was observed at different pH values at a specific temperature by Job's and Ardon's equations. In UPLC, the drug mixture assessment showed that the area of Linagliptin was 2013793, and the area of Azithromycin was 54631 in 50 mg/l. The height of Linagliptin in the drug mixture was 579234, and that of Azithromycin was 11442. For Azithromycin, the wavelength of 731.02 cm-1, 993.34 cm-1, 1379.10 cm-1, and 1718.58 cm-1 decreased in the mixture. Also, for Linagliptin, the wavelength 1363.67 cm-1, 1473.62 cm-1, and 1718.58 cm-1 decreased in the drug mixture. The melting endotherm was 125.55°C, melting normalized energy was -3.0 W/mg, and 225.75°C with melting normalized energy of -5.5 W/mg of the drug mixture as indicated by DSC. In the OGTT test, the blood glucose level of Linagliptin decreased in the drug mixture by 13.58 % and 57.25%. Conclusion: Hence, the concomitant administration of Linagliptin and Azithromycin simultaneously might reduce the therapeutic effect of the drug complex.