COMPARISON OF IMIPENEM PHARMACOKINETICS IN PATIENTS WITH ACUTE OR CHRONIC-RENAL-FAILURE TREATED WITH CONTINUOUS HEMOFILTRATION

The total clearance of imipenem, a carbapenem antibiotic, is reduced from approximately 230 mL/min in patients with normal renal function to approximately 50 mL/min in patients with chronic renal failure. This decline in clearance results not only from the loss of renal clearance, but also from a reduction in the nonrenal clearance from 130 to 50 mL/min. Current dosing recommendations for the administration of imipenem to patients with acute or chronic renal failure are based on this reduced clearance rate. We investigated the pharmacokinetics of imipenem in critically ill patients with acute or chronic renal failure to determine whether published dosing guidelines were applicable to both patient populations. Imipenem pharmacokinetic parameters were determined in 10 anuric patients with renal failure managed by continuous venovenous hemofiltration (CVVH). Seven patients had acute renal failure, while the other three had preexisting chronic renal failure. Imipenem serum concentration data were incorporated into a first-order, single-compartment pharmacokinetic model. Determinations of the area under the serum concentration-time curve were made by the trapezoidal rule. Dosing regimens were calculated from clearance data to achieve a mid-dose imipenem serum concentration of 12 mg/L. The total clearance of imipenem in patients with acute renal failure (108.3 ± 13.8 mL/min; mean ± SD) was significantly greater than the total clearance measured in patients with chronic renal failure (64.4 ± 10.5 mL/min; P < 0.02). This increased clearance resulted from a greater nonrenal clearance of the drug in patients with acute renal failure (95.0 ± 13.8 v 51.1 ± 10.5 mL/min; P < 0.02). The higher clearance rates in the patients with acute renal failure resulted in significantly higher total daily imipenem requirements (1847 ± 243 mg/24 h) as compared with patients with chronic renal failure (1111 ± 183 mg/24 h; P < 0.02). In patients with acute renal failure, a comparison of the non renal clearance rates to the day of CVVH therapy on which the serum concentrations were obtained suggested that imipenem nonrenal clearance declined with the duration of therapy (P < 0.05; r2 = 0.741). The pharmacokinetic parameters of imipenem differ in patients with acute versus chronic renal failure. Consequently, the use of imipenem dosing recommendations, based on data derived from patients with chronic renal failure, may result in inadequate dosing of the drug in patients with acute renal failure. © 1993, National Kidney Foundation. All rights reserved. All rights reserved.