Pharmacokinetics of Cefepime in Patients with Thermal Burn Injury

Abstract

ABSTRACT 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 (CL CR ), total clearance (CL T ), renal clearance (CL R ), alpha phase half-life, beta phase half-life, and volume of distribution at steady state ( V SS ) 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 CL T and CL R in burn patients were similar to previously reported values for healthy volunteers when normalized by CL CR . Stepwise multiple regression was used to associate CL T with CL CR and days postburn ( r 2 = 0.861), CL R with CL CR and days postburn ( r 2 = 0.773), nonrenal clearance with percent third-degree (% 3°) burn and albumin concentration ( r 2 = 0.550), and V SS only with % 3° burn ( r 2 = 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.