Methods Used to Study Drug-drug Interactions: A Review

Abstract

Drug-drug interaction is a pharmacokinetic parameter which, among others, determines the fate of  drugs in giving their therapeutic actions. Most of the drug interactions are studied by using in vitro methods though few in vivo methods are also applied. The review aimed to summarize the different aspects of methods used to study drug-drug interactions. In order to collect relevant data on methods used to study drug-drug interactions, different search engines such as Google Scholar, PubMed, Scopus and Research Gate were used for the literature survey. Alongside these search engines, standard textbooks were also consulted to extract relevant information. The findings revealed the different methods used to study drug-drug, drug-metal and drug-disease interactions. Nine in vitro methods used in drug-drug interaction (DDI) analysis have been thoroughly explained and discussed in this review included: UV-VIS absorption spectral analysis, Conductometric analysis, Ardon’s method, Job’s continuous variation method, Differential Scanning Calorimetry (DSC) thermogram, FTIR spectroscopic investigation, Thin Layer Chromatography technology, all of these were used to detect the interaction between two hypothetical drugs referred to as DRUG A and DRUG B, Fluorescence spectroscopy (used to examine the interaction between tannin and bovine serum albumin), and high-performance liquid chromatography (HPLC) (used to detect the interaction between tramadol and sildenafil). Additionally, in the case of the in vivo method, young healthy animals having different body weights are used. Lastly, three in-silico methods used in drug-drug interaction analysis have been discussed included: Quantitative Structure–Activity Relationship (QSAR) Models, Molecular Docking and Molecular Dynamics (MD) Simulations, and the Physiologically Based Pharmacokinetic (PBPK) Modelling. Overall, the study confirmed Organic Anion Transporting Polypeptide 1B1 (OATP1B1) plays a key role in the pharmacokinetic behaviour of the statins and serves as a useful indicator for identifying transporter mediated drug-drug interactions. Therefore, incorporating OATP1B1 assessment into DDI studies is essential to enhance prediction reliability and to improve drug safety profiles.