In this study, the in vitro interaction of epirubicin (EPR), a cytostatic antibiotic, with plasma proteins (PP), namely alpha-HSA, gamma-HSG, alpha+beta-HSG and with isolated human red blood cells (RBCs) was investigated and further correlated with the in vivo pharmacokinetics and binding of EPR and two of its metabolites, 13-dihydroepirubicin and 7-deoxydoxorubicinone to RBCs. The in vitro encapsulation rate in isolated erythrocytes amounts to 52.9 +/- 2.8% and remains constant within the range of studied concentrations (2.5-20 micrograms/ml). EPR was found to bind differently to the various PP in vitro. Binding to alpha-HSA amounted up to 51.0 +/- 7.10%, to alpha+beta-HSG 79.45 +/- 2.7%, to gamma-HSG 57.1 +/- 2.8%. The in vivo-binding rate of EPR, dihydroepirubicin and deoxydoxorubicinone to RBCs after 5 min of injection was 32 +/- 6.96%, 11.6 +/- 3.1% and 10.05 +/- 3.5% respectively, their availability in serum was 42.6 +/- 11.8%, 2.4 +/- 0.4% and 1.2 +/- 0.67% respectively.