Influence of sulfaethidole on the human pharmacokinetics of dicloxacillin

In a five-patient crossover study, serum levels of dicloxacillin after intravenous administration of dicloxacillin in the absence and presence of sulfaethiodole were measured. Significantly greater serum concentrations of dicloxacillin were noted when dicloxacillin was administered with sulfaethidole. Pharmacokinetic evaluation of the data suggests that the higher serum concentrations were primarily the result of changes in the extravascular distribution for dicloxacillin in the presence of sulfaethidole. Although examination of the distribution rate constants for dicloxacillin in a two-compartment open model would suggest a lowering of serum concentrations, the experimental data clearly indicate that the serum and tissue compartment dicloxacillin concentrations increased in the presence of sulfaethiodle, indicating that protein binding in the central as well as extravascular compartments could be affected by sulfaethidole.