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

J Clin Pharmacol. 2003 Dec;43(12):1329-40. doi: 10.1177/0091270003260286.

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.

Publication types

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

MeSH terms

  • Acute Kidney Injury / drug therapy
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / mortality
  • Aged
  • Area Under Curve
  • Critical Care
  • Drug Administration Schedule
  • Female
  • Half-Life
  • Hemodiafiltration*
  • Humans
  • Male
  • Meropenem
  • Metabolic Clearance Rate
  • Middle Aged
  • Models, Biological
  • Thienamycins / administration & dosage
  • Thienamycins / pharmacokinetics*
  • Thienamycins / therapeutic use

Substances

  • Thienamycins
  • Meropenem