Imipenem pharmacokinetics in patients with burns

The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of HPLC. A two-compartment model provided a superior fit to the data compared with a one-compartment model in 9 of the 11 patients. There was no significant difference in any pharmacokinetic parameter between the initial dose and after multiple dosing (p > 0.05). Combined mean (±SD) parameter estimates for the two dosing periods were as follows: Vc, 0.11 ± 0.06 L/kg; Vss, 0.22 ± 0.06 L/kg; CL, 12.5 ± 3.6 L/hr/1.73 m2; t½α, 0.18 ± 0.13 hr; t½β, 1.12 ± 0.44 hr. Mean clearance in two patients with creatinine clearance values >150 ml/min/1.73 m2was 17.7 L/hr/1.73 m2. Mean clearance in two patients with creatinine clearance values <50 ml/min/1.73 m2 was 8.5 L/hr/1.73 m2. No pharmacokinetic parameter was significantly different from previously reported parameters in normal volunteers (p > 0.05). Creatinine clearance ranged from 17 to 218 ml/min/1.73 m2. Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.0001). No significant association was found between total body surface area burns and imipenem clearance (p > 0.05). Our data suggest imipenem pharmacokinetics in patients with burns are comparable to those in normal volunteers although substantial intersubject variability exists. Measured creatinine clearance values may be useful in estimating imipenem clearance clinically. Clinical Pharmacology and Therapeutics (1990) 48, 130–137; doi:10.1038/clpt.1990.127