Red blood cell partitioning, protein binding and lipophilicity of six phenothiazines

Hexane-water partition coefficients, pKa values, protein binding and red blood cell partitioning were studied with six phenothiazine drugs. Red cell partitioning was independent of drug concentration, and there was no correlation between partitioning and physicochemical characteristics. Red cell partitioning could be used indirectly to estimate protein binding, but two potential pitfalls of general importance were found. Failure to consider drug binding of glassware and haematocrit changes were shown to induce incorrect estimates of both red cell partitioning and protein binding, as well as hexane-water partition coefficients.