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Pharmacokinetics and Dosage Adaptation of Meropenem during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

From the Division of Clinical Pharmacology (C. Robatel, L. A. Decosterd, J. Biollaz, T. Buclin) and the Division of Intensive Care Medicine (P. Eckert, M. D. Schaller), Department of Medicine, University Hospital, Lausanne, Switzerland.

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.

Key Words: Continuous venovenous hemodiafiltration • meropenem • acute renal failure • pharmacokinetics

Address for reprints: T. Buclin, MD, Division of Clinical Pharmacology and Toxicology, Hôpital Beaumont 6^ème étage, 1011 Lausanne-CHUV, Switzerland.

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