Interaction of beta-lactam antibiotics on bilirubin-albumin complex: comparison by three methods, total bilirubin, unbound bilirubin and erythrocyte-bound bilirubin

The effects of 'third-generation' cephalosporins and penicillin analogues on the concentrations of total unconjugated bilirubin, unbound bilirubin and erythrocyte-bound bilirubin were determined in blood samples. This study was performed, in vitro, at two bilirubin/albumin molar ratios and at various concentrations of antibiotics. The most effective displacers, considering the three methods, were antibiotics tightly bound to albumin: ceftriaxone and cefotetan. Cefoperazone, which is bound to albumin as tightly as these two antibiotics, caused no significant increase in unbound bilirubin but should be considered as a displacer drug on the basis of the variations of erythrocyte-bound bilirubin and total bilirubin. We suggest that drug interaction on bilirubin-albumin binding be investigated by several methods.