Pharmacokinetics and pharmacodynamics of ceftizoxime in patients with dosages adjusted for renal function

Study Objective. Our institution developed dosing guidelines for patients w ith renal impairment based on pharmacokinetic data and class-specific pharm acodynamics. Ceftizoxime was chosen as a model agent to evaluate if the mod ified guidelines achieved similar minimal plasma concentration (Cp-min) and time above the minimum inhibitory concentration of the infecting organism (T>MIC) in patients with renal impairment versus those with normal renal fu nction. Design. Prospective pharmacokinetic and pharmacodynamic evaluation of cefti zoxime dosages. Setting. University-affiliated hospital. Patients. Forty-three patients with suspected or documented infection were enrolled and classified into four groups based on creatinine clearance (Cl- cr; ml/min): group 1, above 100; group 2, 61-99; group 3, 31-60; and group 4, 15-30. Interventions, Ceftizoxime serum concentrations were obtained at steady sta te. Measurements and Main Results. Pharmacokinetic and pharmacodynamic paramete rs were calculated, As expected, clearance and elimination rate constant we re reduced, and half-life tended to be greater in patients with renal impai rment. The Cp-min and area under the concentration-time curve over 24 hours were similar between groups (p=0.39, p=0.42). The T>MIC was 100% for all p atient isolates, and 90% or more versus our clinical strain for all groups. Clinical outcomes were similar among all groups. Conclusion. Our dosing guidelines achieved similar Cp-min among all groups of patients. Our results support that recommendations for dosing adjustment s should be based on pharmacokinetic data and must also consider pharmacody namic parameters.