Pharmacokinetics and dosage adaptation of meropenem during continuous venovenous hemodiafiltration in critically ill patients

Details

Serval ID
serval:BIB_FB70FDC0E665
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pharmacokinetics and dosage adaptation of meropenem during continuous venovenous hemodiafiltration in critically ill patients
Journal
Journal of Clinical Pharmacology
Author(s)
Robatel  C., Decosterd  L. A., Biollaz  J., Eckert  P., Schaller  M. D., Buclin  T.
ISSN
0091-2700 (Print)
Publication state
Published
Issued date
12/2003
Volume
43
Number
12
Pages
1329-40
Notes
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Abstract
Meropenem, a carbapenem broad-spectrum antibiotic, is regularly used in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). Its disposition was studied over one dosage interval in 15 patients under CVVHDF on a steady regimen of 500 or 1000 mg every 8 to 12 hours. Meropenem levels were measured in plasma and filtrate-dialysate by high-performance liquid chromatography (HPLC) with UV detection. The mean CVVHDF flow rates were 7.1 +/- 0.9 L/h for blood (mean +/- SD), 0.5 +/- 0.3 L/h for predilution solution, 1.2 +/- 0.3 L/h for countercurrent dialysate, and 1.8 +/- 0.5 L/h for the total filtrate-dialysate. The pharmacokinetic analysis was based both on a noncompartmental approach and on a four-compartment modeling. The mean (coefficient of variation [CV]) total body clearance, volume of distribution at steady state, and mean residence time were, respectively, 5.0 L/h (46%), 14.3 L (29%), and 4.8 h (36%). The hemodiafiltration clearances calculated from plasma data alone and plasma with filtrate-dialysate data were 1.2 L/h (26%) and 1.6 L/h (39%), respectively. The compartmental model was used to optimize the therapeutic schedule of meropenem, considering reference minimal inhibitory concentration (MIC) of sensitive strains (4 mg/L). The results indicate that two different therapeutic schedules of meropenem are equally applicable to patients receiving CVVHD: either 750 mg tid or 1500 bid.
Keywords
Aged Area Under Curve Critical Care Drug Administration Schedule Female Half-Life *Hemodiafiltration Humans Kidney Failure, Acute/drug therapy/*metabolism/mortality Male Metabolic Clearance Rate Middle Aged Models, Biological Thienamycins/administration & dosage/*pharmacokinetics/therapeutic use
Pubmed
Web of science
Create date
25/01/2008 10:41
Last modification date
20/08/2019 16:26
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