Amikacin Pharmacokinetics During Continuous Veno-Venous Hemodialysis

Abstract

IntroductionLittle is known about the pharmacokinetics of amikacin during continuous renal replacement therapy.MethodsThis prospective observational study included patients admitted to an academic medical center who received amikacin therapy while on continuous veno-venous hemodialysis (CVVHD) and had at least two serum sample concentrations measured after first-dose administration. First-order pharmacokinetic parameters, patient characteristics, and CVVHD parameters were recorded.ResultsFifteen patients were included in the analysis. The median (interquartile range) dose of amikacin and dialysate flow rate, based on adjusted body weight, were 14.1 mg/kg (11.7–17.3 mg/kg) and 23.9 mL/kg/h (19.0–29.5 mL/kg/h), respectively. This corresponded with a median Cmax of 28.5 μg/mL (20.9–39.0 μg/mL). There was a significant correlation between clearance and dialytic dose (for every 1 L/h increase in dialysate flow rate, clearance rate increased by 23.6 mL/min [95% confidence interval 1.7–45.4 mL/min; P = 0.037]).ConclusionThe results of this study suggest that amikacin dose and interval should be individualized for each patient on CVVHD based on first-dose pharmacokinetic assessment.

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy

“…Ultrafiltration rate: 1,900-3,250 ml/h 1 g q8h (Vossen et al, 2015) Dialysate rate: 2 L/h 1 g q8h (Vossen et al, 2015) Combined flow rate: 1,500-2,800 ml/h 1 g q8h (Vossen et al, 2015) Amikacin Ultrafiltration rate: 30 ml/kg/h 25 mg/kg q48h (Roger et al, 2016b) Exact dose cannot be predicted (Lam and Bauer, 2013) Combined flow rate: 30 ml/kg/h 25 mg/kg q48h (Roger et al,…”

“…A strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring should be the preferred approach for amikacin under CVVH and CVVHDF (30 ml/kg/h) (Roger et al, 2016b). Studies (Lam and Bauer, 2013) observed a wide range of C max and T 1/2 during CVVHD, and indicated that the exact amikacin dosing regimen cannot be accurately predicted based on the dialytic dose or other factors available at the bedside during CVVHD. Amikacin dose regimens should be individualized for each patient on CVVHD based on first-dose PK assessment.…”

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

“…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).…”

Population Pharmacokinetic Study of the Suitability of Standard Dosing Regimens of Amikacin in Critically Ill Patients with Open-Abdomen and Negative-Pressure Wound Therapy

“…This specific population was characterized by a wide interindividual variability of pharmacokinetics parameters. On the one hand, the total volume of distribution in non-CRRT and CRRT patients was higher than most of the previously reported values in critically ill patients (Table 5) (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). The increased distribution was mainly reflected in the central volume and probably related to the limited diffusion of amikacin in peritoneal tissue (25).…”