New aspects of free drug concentration determination in human serum with equilibrium dialysis

The effect of the anticoagulants heparin and citrate on the albumin binding of warfarin in plasma has been studied by means of equilibrium dialysis. Heparin and citrate were found to decrease the free concentration of warfarin in plasma at a given total concentration of the drug, heparin by elevating the non-esterified fatty acid concentration in plasma and citrate by shifting the N in equilibrium with B equilibrium towards the B conformation of albumin. In cases where free concentrations of warfarin in vivo are to be determined, it is therefore preferable to use serum instead of plasma. When free serum levels of drugs are determined by equilibrium dialysis, it is advisable to use the ultrafiltrate of (drug free) serum as dialysis fluid. The importance of the composition of the dialysis fluid for the determination of serum levels of free drugs other than warfarin is discussed.