Pharmacokinetics and pharmacodynamics of imipenem during continuous renal replacement therapy in critically ill patients

Antimicrob Agents Chemother. 2005 Jun;49(6):2421-8. doi: 10.1128/AAC.49.6.2421-2428.2005.


The pharmacokinetics of imipenem were studied in adult intensive care unit (ICU) patients during continuous venovenous hemofiltration (CVVH; n=6 patients) or hemodiafiltration (CVVHDF; n=6 patients). Patients (mean+/-standard deviation age, 50.9+/-15.9 years; weight, 98.5+/-15.9 kg) received imipenem at 0.5 g every 8 to 12 h (total daily doses of 1 to 1.5 g/day) by intravenous infusion over 30 min. Pre- and postmembrane blood (plasma) and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, and 8 or 12 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL(S)) and elimination half-life (t1/2) of imipenem were 145+/-18 ml/min and 2.7+/-1.3 h during CVVH versus 178+/-18 ml/min and 2.6+/-1.6 h during CVVHDF, respectively. Imipenem clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 25% and 32% of CL(S), respectively. The results of this study indicate that CVVH and CVVHDF contribute to imipenem clearance to a greater degree than previously reported. Imipenem doses of 1.0 g/day appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC up to 2 microg/ml) during CVVH or CVVHDF, but doses of 2.0 g/day or more may be required to adequately treat and prevent resistance in pathogens with higher MICs (MIC=4 to 8 microg/ml). Higher doses should only be used after consideration of potential central nervous system toxicities or other risks of therapy in these severely ill patients.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use*
  • Cilastatin / administration & dosage
  • Cilastatin / therapeutic use
  • Critical Illness
  • Drug Therapy, Combination
  • Female
  • Hemodiafiltration
  • Hemofiltration
  • Humans
  • Imipenem / pharmacokinetics*
  • Imipenem / therapeutic use*
  • Kidney Failure, Chronic / drug therapy
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Prospective Studies
  • Protease Inhibitors / administration & dosage
  • Protease Inhibitors / therapeutic use
  • Renal Replacement Therapy*


  • Anti-Bacterial Agents
  • Protease Inhibitors
  • Cilastatin
  • Imipenem