Influence of renal replacement modalities on amikacin population pharmacokinetics in critically ill patients on continuous renal replacement therapy

摘要

The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean +/- standard deviation parameter estimates were 25.2 +/- 17.3 liters for the central volume, 0.89 +/- 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 +/- 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 +/- 2.35 liters/h for hemodiafiltration clearance, and 4.69 +/- 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (>= 25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (C-max)/MIC ratio of >= 8 and a minimal concentration of