Drug Interaction with Inhibitors: Prediction of Exposure of Drugs Following Drug-Inhibitor Interaction Based on Molecular Weight Ratio

These days, chemical descriptors such as molecular weight (MW) and logarithmic partition coefficient (logP) for the prediction of exposure (AUC) of drugs for drug-drug interaction (DDI) studies is drawing attention. These methods allow efficient screening tool for DDI studies and are also time and cost-effective. The objective of this study is to develop a simple quantitative method to predict AUC of P-glycoproteins (P-gP) and non-P-gp drugs following interaction studies with inhibitor(s). The AUC of a drug following inhibition was predicted by using the ratio of the MW of two interacting drugs as following. Predicted AUC = AUC of a drug before inhibition/ratio of the MW. The impact of several strong or moderate inhibitors was evaluated on 76 P-gP and non-P-gp drugs. There were 119 and 38 observations(data points) for p-gp and non-P-gp drugs, respectively. The total number of observations (data points) was 157. Out of 157 observations, 141 (89.8%), 129 (82.2%), and 85 (54.1%) observations were within 0.5-2-fold, 0.5-1.5-fold, and 0.7-1.3-fold prediction error, respectively. The average absolute fold-error (AFE) was 0.95. Overall, the predictive power of the proposed method for DDI following the administration of inhibiters was found to be a suitable and to a great extent accurate approach when compared with the observed clinical data. The proposed method does not require extensive data such as in-vitro data, many physical or chemical properties or extensive physiological parameters. The proposed method is suitable for subsequent clinical trials or in some cases may be used in clinical settings.