Pharmacokinetics and pharmacodynamics of ceftizoxime in patients with dosages adjusted for renal function.
OBJECTIVE
Our institution developed dosing guidelines for patients with renal impairment based on pharmacokinetic data and class-specific pharmacodynamics. Ceftizoxime was chosen as a model agent to evaluate if the modified 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 function.


METHODS
Prospective pharmacokinetic and pharmacodynamic evaluation of ceftizoxime dosages.


METHODS
University-affiliated hospital.


METHODS
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.


METHODS
Ceftizoxime serum concentrations were obtained at steady state.


RESULTS
Pharmacokinetic and pharmacodynamic parameters were calculated. As expected, clearance and elimination rate constant were reduced, and half-life tended to be greater in patients with renal impairment. 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 patient isolates, and 90% or more versus our clinical strain for all groups. Clinical outcomes were similar among all groups.


CONCLUSIONS
Our dosing guidelines achieved similar Cp(min) among all groups of patients. Our results support that recommendations for dosing adjustments should be based on pharmacokinetic data and must also consider pharmacodynamic parameters.
Neuhauser
M M
MM
Department of Pharmacy Services, Detroit Receiving Hospital and University Health Center, Michigan 48201, USA.
McKinnon
P S
PS
Hershberger
E
E
Rybak
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001424:Bacterial Infections / Q000188:drug therapy; D015296:Ceftizoxime / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000378:metabolism*; D018709:Statistics, Nonparametric
D002511:Cephalosporins; D015296:Ceftizoxime