Evaluation of competitive binding interaction of neratinib and tamoxifen to serum albumin in multidrug therapy'

Co-administration of two drugs to obtain a therapeutic goal is a common practice clinically and for effective use of drug therapy. However, the co-administration can sometimes cause adverse effects due to pharmacokinetic drug interactions. Breast Cancer treatment regimen include tyrosine kinase inhibitor neratinib (NRB) and/or tamoxifen (TMX). In this study neratinib and tamoxifen interaction with bovine serum albumin (BSA) and human serum albumin (HSA) individually and in combination using fluorescence spectroscopy was studied. The aim of this study was to find out whether there is a possibility of either of the two drugs interfering in the plasma protein binding of the other drug. Subdomain IIA of both the BSA and HSA was found to bind tamoxifen and neratinib. The lambda(ex) = 280 nm and 295 nm were used for the analysis of neratinib-SA, tamoxifen-SA, neratinib: SA in presence of constant concentration of tamoxifen and similarly tamoxifen-SA in presence of constant concentration of neratinib. The interaction study of the binary and the ternary systems suggest that neratinib doesn't affect the interaction between SA and tamoxifen. In contrast, the interaction between neratinib and SA was affected by tamoxifen. The binding constant and quenching constant values suggest that tamoxifen dislodges neratinib from its serum albumin complex whereas neratinib doesn't affect the interaction between SA and tamoxifen. Thus, it was concluded from the results the study that during simultaneous administration of neratinib and tamoxifen, their competition for the SA binding sites should be taken into account. (C) 2019 Elsevier B.V. All rights reserved.