Human Albumin Binding of Tamoxifen in the Presence of a Perfluorochemical Erythrocyte Substitute

Abstract

The binding of tamoxifen (an HSA site IV ligand) to human serum albumin (HSA) in the presence of a perfluorochemical (PFC) erythrocyte substitute has been examined. Standard centrifugation followed by supernatant ultrafiltration was used to study the binding of 0.1 and 0.5 microgram mL-1 tamoxifen at ambient conditions. Tamoxifen was extensively bound (greater than 99%) to the PFC emulsion through an association with the emulsifiers of the droplets. Tamoxifen was also extensively bound (greater than 99%) to HSA. The percent free tamoxifen increased upon HSA dilution. Tamoxifen was extensively bound by various mixtures of HSA and the PFC emulsion and the percent free drug was similar to those obtained with HSA alone. However, the position of drug binding (PFC emulsion vs HSA) varied significantly with changes in the ratio of PFC emulsion to HSA. This could be important in terms of the different distribution of HSA and PFC emulsion in the body. Studies with PFC emulsion components indicated that any displacement of HSA-bound tamoxifen by the PFC emulsion was due to the oleic acid and, to a much smaller degree, Pluronic F-68 components. Other HSA site IV ligands are expected to be similarly displaced.