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Antimicrobial Agents and Chemotherapy, December 1999, p. 2848-2854, Vol. 43, No. 12
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Pharmacokinetics of Cefepime in Patients with Thermal Burn Injury

Charles R. Bonapace,1 Roger L. White,1 Lawrence V. Friedrich,1 E. Douglas Norcross,2 and John A. Bosso1,*

Anti-Infective Research Laboratory, College of Pharmacy,1 and the Department of Surgery, College of Medicine,2 Medical University of South Carolina, Charleston, South Carolina

Received 25 January 1999/Returned for modification 17 May 1999/Accepted 23 August 1999

The pharmacokinetics of cefepime following administration of a single 2-g dose were evaluated for 12 adult patients with thermal burn injury and suspected or documented infection. Serial blood and urine samples for cefepime concentration determination were obtained for 24 h following drug administration. Serum and urine cefepime concentrations were determined by high-performance liquid chromatography and serum concentrations were fit to a two-compartment pharmacokinetic model. Mean (standard deviation [SD]) age, actual body weight (ABW), percent total body surface area burned, and days postburn at the time of study were 41 (13) years, 84 (22) kg, 36 (17)%, and 9 (3) days, respectively. Mean (SD) measured creatinine clearance (CLCR), total clearance (CLT), renal clearance (CLR), alpha phase half-life, beta phase half-life, and volume of distribution at steady state (VSS) were 135 (31) ml/min, 8.8 (2.4) liters/h, 8.1 (2.0) liters/h, 0.33 (0.14) h, 2.8 (0.6) h, and 0.43 (0.10) liters/kg ABW, respectively. Cefepime CLT and CLR in burn patients were similar to previously reported values for healthy volunteers when normalized by CLCR. Stepwise multiple regression was used to associate CLT with CLCR and days postburn (r2 = 0.861), CLR with CLCR and days postburn (r2 = 0.773), nonrenal clearance with percent third-degree (% 3°) burn and albumin concentration (r2 = 0.550), and VSS only with % 3° burn (r2 = 0.624). Simulated steady-state serum concentrations obtained by using the patients' pharmacokinetic parameters exceeded the susceptibility interpretive standard (breakpoint) of cefepime for at least 60% of the dosing interval with dosing regimens of 1 g every 8 h (q8h), 2 g q8h, and 2 g q12h. Despite differences in pharmacokinetic parameters between our patients and healthy volunteers, it appears that these dosing regimens may be adequate in similar burn patients.


* Corresponding author. Mailing address: Anti-Infective Research Laboratory, Medical University of South Carolina, College of Pharmacy, 280 Calhoun St., P.O. Box 250140, Charleston, SC 29425. Phone: (843) 792-8501. Fax: (843) 792-1617. E-mail: bossoja{at}musc.edu.


Antimicrobial Agents and Chemotherapy, December 1999, p. 2848-2854, Vol. 43, No. 12
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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