title: Pharmacokinetics of Imipenem/Cilastatin Burn Intensive Care Unit Patients Undergoing High-Dose Continuous Venovenous Hemofiltration.
abstract: High-dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high-dose CVVH.
  
  
  
  Prospective clinical pharmacokinetic study.
  
  
  
  Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied.
  
  
  
  Blood and effluent samples for analysis of I/C concentrations were collected for up to 6 hours after the I/C infusion for calculation of I/C total CL (CLTotal), CL by CVVH (CLHF), half-life during CVVH, volume of distribution at steady state (Vdss), and the percentage of drug eliminated by CVVH.
  
  
  
  In this patient sample, the mean age was 50 ± 17 years, total body surface area burns was 23 ± 27%, and 80% were male. Nine patients were treated with high-dose CVVH for acute kidney injury and one patient for sepsis. The mean delivered CVVH dose was 52 ± 14 ml/kg/hour (range 32-74 ml/kg/hr). The imipenem CLHFwas 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CLTotal(14.74 ± 4.75 L/hr). Cilastatin CLHFwas 1.98 ± 0.56 L/hour, which accounted for 45 ± 19% of the CLTotal(5.16 + 2.44 L/hr). The imipenem and cilastatin half-lives were 1.77 ± 0.38 hours and 4.21 ± 2.31 hours, respectively. Imipenem and cilastatin Vdsswere 35.1 ± 10.3 and 32.8 ± 13.8 L, respectively.
  
  
  
  Efficient removal of I/C by high-dose CVVH, a high overall clearance, and a high volume of distribution in burn intensive care unit patients undergoing this CRRT method warrant aggressive dosing to treat serious infections effectively depending on the infection site and/or pathogen.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Boucher
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Joanna Q
authors.initials: JQ
authors.lastname: Hudson
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.|Firefighters' Regional Burn Center, Regional One Health, Memphis, Tennessee.
authors.forename: David M
authors.initials: DM
authors.lastname: Hill
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Swanson
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: G Christopher
authors.initials: GC
authors.lastname: Wood
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: S Casey
authors.initials: SC
authors.lastname: Laizure
authors.affiliation: Firefighters' Regional Burn Center, Regional One Health, Memphis, Tennessee.|Department of Plastic Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Angela
authors.initials: A
authors.lastname: Arnold-Ross
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Zhe-Yi
authors.initials: ZY
authors.lastname: Hu
authors.affiliation: Firefighters' Regional Burn Center, Regional One Health, Memphis, Tennessee.|Department of Plastic Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: William L
authors.initials: WL
authors.lastname: Hickerson
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015377:Cilastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006440:Hemofiltration / Q000379:methods*; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination
keywords: burns; cilastatin; continuous hemofiltration; imipenem; pharmacokinetics; renal replacement therapy