Pharmacokinetics of a loading dose of amikacin in septic patients undergoing continuous renal replacement therapy

Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy

“…Our results showed that the PK/PD targets (C max /MIC ratio Ն 8, AUC/MIC Ն 70) were achieved with a dosing regimen of 25 mg/kg or higher in critically ill patients undergoing CVVH or CVVHDF. These results are consistent with those reported by Taccone et al (11). They reported that a 25-mg/kg loading dose of amikacin in patients undergoing CVVHDF at a dose of 30 ml/kg/h and a blood flow rate setting at 150 to 200 ml/min achieved the targeted C max of 64 mg/liter in 9 (69%) pa- tients.…”

“…In a previous study, we highlighted that the use of a regimen with a higher dose (30 mg/kg) in association with therapeutic drug monitoring led to extended dosing intervals in half of the critically ill patients studied (28). Taccone et al reported that the median time to achieve a trough concentration below 5 mg/liter was 36 h (IQR, 14 to 76 h) in patients undergoing CVVHDF (11). The extended dosing in- tervals suggested by the results of the present study are consistent with recommendations for aminoglycoside dosing regimens in critically ill patients receiving continuous RRT (30)(31)(32).…”

“…They reported that a 25-mg/kg loading dose of amikacin in patients undergoing CVVHDF at a dose of 30 ml/kg/h and a blood flow rate setting at 150 to 200 ml/min achieved the targeted C max of 64 mg/liter in 9 (69%) pa- tients. The amikacin clearance reported in that study widely varied between 0.006 and 0.198 liter/kg/h, but the mean clearance of amikacin was lower than that reported in the present study (11). The authors did not find any correlation between RRT settings and amikacin clearance.…”

“…In previous studies with intensive care unit (ICU) patients undergoing CRRT, amikacin clearance varied from 0.53 to 5.34 liters/h, accounting for 40 to 89% of the total body clearance (10)(11)(12)(13)(14)(15). These studies also reported conflicting results on the correlation between drug clearance and CRRT settings (11,14).…”

“…These studies also reported conflicting results on the correlation between drug clearance and CRRT settings (11,14). As a general rule, it is expected that the efficiency of drug removal would be higher in continuous venovenous hemodiafiltration (CVVHDF; diffusive and convective technique) modalities than in continuous venovenous hemofiltration (CVVH; convective technique) modalities (16).…”