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Antimicrobial Agents and Chemotherapy, June 2003, p. 1853-1861, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.1853-1861.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics and Pharmacodynamics of Cefepime in Patients with Various Degrees of Renal Function

Vincent H. Tam,1,2,{dagger} Peggy S. McKinnon,1,3 Ronda L. Akins,1,3,{ddagger} George L. Drusano,2 and Michael J. Rybak1,3,4*

Department of Pharmacy Services, Detroit Receiving Hospital and University Health Center, Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences,1 ,3 School of Medicine, Wayne State University, Detroit, Michigan 48201,4 Division of Clinical Pharmacology, Clinical Research Institute, Albany Medical College, Albany, New York 122082

Received 17 January 2002/ Returned for modification 16 September 2002/ Accepted 5 March 2003

This study evaluated the pharmacokinetics of cefepime in 36 patients with different levels of renal function. Pharmacokinetic and pharmacodynamic parameters were calculated using samples obtained at steady state. Patients with creatinine clearance (CLCR) of >100 ml/min had more rapid clearance (CL) and a lower minimum concentration in serum (Cmin). Cmin in this group was found to be 3.3 ± 3.6 mg/liter (mean and standard deviation), compared to 19.5 ± 21.5 mg/liter in patients with a CLCR of between 60 and 100 ml/min (P = 0.025) and 14.0 ± 11.5 mg/liter in patients with a CLCR of <60 ml/min (P = 0.009). Patient data were also analyzed by the nonparametric expectation maximization method and Bayesian forecasting. The median volume of distribution in the central compartment was 27.08 liters. CL and CLCR were highly correlated (P = 0.00033) according to the equation CL= 0.324 liters/h + (0.0551 x CLCR). The median rate constants from the central compartment to the peripheral compartment and from the peripheral compartment to the central compartment were 12.58 and 41.09 h-1, respectively. The time-concentration profiles for 1,000 patients (CLCRs, 120, 60, and 30 ml/min) each receiving various dosing regimens were simulated by using Monte Carlo simulations. Standard dosing resulted in a Cmin that was greater than or equal to the MIC in more than 80% of the simulated profiles with MICs <=2 mg/liter. Current dosing recommendations may be suboptimal for monotherapy of infections due to less susceptible pathogens (e.g., those for which MICs are >=4 mg/liter), particularly when CLCR exceeds 120 ml/min.

* Corresponding author. Mailing address: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Appelbaum College of Pharmacy and Health Sciences, 259 Mack Ave., Detroit, MI 48201. Phone: (313) 577-4376. Fax: (313) 577-8915. E-mail: m.rybak{at}wayne.edu.

{dagger} Present address: Department of Clinical Sciences and Administration, College of Pharmacy, University of Houston, Houston, TX 77030.

{ddagger} Present address: Department of Pharmacy Practice, School of Pharmacy, Texas Tech University, Amarillo, TX 79106.

Antimicrobial Agents and Chemotherapy, June 2003, p. 1853-1861, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.1853-1861.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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