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- Title
Pharmacokinetics of Imipenem/Cilastatin Burn Intensive Care Unit Patients Undergoing High-Dose Continuous Venovenous Hemofiltration.
- Authors
Boucher, Bradley A.; Hudson, Joanna Q.; Hill, David M.; Swanson, Joseph M.; Wood, G. Christopher; Laizure, S. Casey; Arnold ‐ Ross, Angela; Hu, Zhe ‐ Yi; Hickerson, William L.
- Abstract
Study objective 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. Design Prospective clinical pharmacokinetic study. Patients Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied. Methods 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. Results 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 CLHF was 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CLTotal (14.74 ± 4.75 L/hr). Cilastatin CLHF was 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 Vdss were 35.1 ± 10.3 and 32.8 ± 13.8 L, respectively. Conclusion 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.
- Subjects
PHARMACOKINETICS; BURN patients; IMIPENEM; CILASTATIN; TREATMENT for burns &; scalds; INTENSIVE care patients; BLOOD filtration; THERAPEUTICS
- Publication
Pharmacotherapy, 2016, Vol 36, Issue 12, p1229
- ISSN
0277-0008
- Publication type
Article
- DOI
10.1002/phar.1866