Influence of fever on cefazolin pharmacokinetics

The influence of fever on the pharmacokinetics of cefazolin was investigate d in patients with acute febrile diseases. Nine patients were included in t he study. Antibiotic serum concentrations were determined using high perfor mance liquid chromatograpy (HPLC). An analog computer and the SIMULINK soft ware package were used to identify the pharmacokinetic model and PCNONLIN s oftware package to obtain the secondary parameters, In 6 patients a two-com partment pharmacokinetic model of cefazolin was observed during fever and a fter defervescence. In 2 patients a two-compartment model changed to a one- compartment after defervescence, and a one-compartment model was observed i n one patient during both periods, Cefazolin-treated patients with a two-co mpartment model (6/9) had higher C-max, mean steady state serum concentrati ons (C-ss), and area under the plasma concentration-time curve (AUC(0-->inf inity)), Smaller central compartment volume (V-1), and lower clearance (Cl) during fever. The varying distribution of antibiotics during fever probabl y reflects different hemodynamic responses to fever.