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Antimicrobial Agents and Chemotherapy, December 1999, p. 2848-2854, Vol. 43, No. 12
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.
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Pharmacokinetics of Cefepime in Patients with Thermal Burn
Injury
*
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.
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