Pharmacokinetics and dosage adaptation of meropenem during continuous venovenous hemodiafiltration in critically ill patients.
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.
Robatel
C
C
Division of Clinical Pharmacology, Department of Medicine, University Hospital, Lausanne, Switzerland.
Decosterd
L A
LA
Biollaz
J
J
Eckert
P
P
Schaller
M D
MD
Buclin
T
T
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D000368:Aged; D019540:Area Under Curve; D003422:Critical Care; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D000077731:Meropenem; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D013845:Thienamycins; D000077731:Meropenem