Interactions on in vitro Serum Protein Binding between Cefpiramide and Three Drugs (Phenytoin, Valproic Acid and Salicylic Acid)

Cefpiramide (CPM) is a third-generation cephem antibiotic characterized by its higher protein binding percentage, higher therapeutic concentration and longer biological half-life. We studied drug interactions of human serum protein binding between CPM and phenytoin (PHT), valproic acid (VPA) and salicylic acid (SA) with higher protein binding percentages. When CPM and SA were added to serum concomitantly, the percentages of the unbound concentration (free percent) of both drugs increased significantly over that of CPM or SA alone. However, when CPM and PHT were added similarly and also when CPM and VPA added in the same way, the free percentages of both drugs did not change significantly. These results confirmed the necessity to pay close attention to the interaction of serum protein binding between CPM and SA because increases in the free percentages of both drugs may adversely influence the clinical effects and therapeutic safety.