Quantitative calorimetric and spectroscopic analysis of drug-drug interactions

Abstract

Quantitative study of drug-drug interaction (DDI) is important for their effective and safe clinical management of various diseases. The interaction between two drugs results in either a reduction in action of one drug or an overall enhancement of the patient-beneficial effect. In the present work, we have studied interaction of naproxen with various anticancer, non-steroidal anti-inflammatory drugs, vitamins, antibiotic, antidiabetic, and antithyroid drugs with the help of ultrasensitive isothermal titration calorimetry and uv-absorbance spectroscopy. The purpose of this research is to comprehend the strength of drug-drug interaction based on thermodynamic signatures and simultaneously obtain support from absorbance spectral changes. Weak interaction of naproxen was observed with all the studied drugs except for L-ascorbic acid, diclofenac and lincomycin. In all the discussed drugs L-Ascorbic acid has the strongest interaction with naproxen while diclofenac and lincomycin show no sign of interaction. Further, correlation of standard molar enthalpy of interaction (ΔHm°), change in absorbance maxima (ΔAmax), and partitioning coefficient in organic to aqueous phase (logP) with number of H-bonding groups present (nH) on the drug was done, which suggests that with increase in hydrogen bonding groups the strength of DDI decreases. The thermodynamic signature also enabled understanding role of desolvation in the interaction process.