Amikacin Pharmacokinetics During Continuous Veno-Venous Hemofiltration

Robert, R.; Rochard, E.; Malin, F.; Bouquet, S.

doi:10.1097/00003246-199104000-00029

Cited by 16 publications

(9 citation statements)

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“…Several studies have reported that the pharmacokinetics of aminoglycosides are altered in critically ill patients, leading to a C max lower than the targeted C max in 30 to 40% of critically ill patients using standard dosing regimens (24)(25)(26)(27). The increased volume of distribution observed in critically ill patients and the concentration-dependent killing activity of aminoglycosides support the use of regimens with higher doses of amikacin to achieve adequate C max s. The use of dosing regimens of Ն25 mg/kg in critically ill patients has been suggested by several authors and recommended by some national guidelines (13,24,27,28). However, some concerns remain about aminoglycoside-related nephrotoxicity using high aminoglycoside dosing regimens, especially in patients with AKI requiring RRT.…”

Section: Discussionmentioning

confidence: 99%

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

Roger

Wallis

Muller

et al. 2016

Antimicrob Agents Chemother

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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 (CV-VHDF). 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.

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Section: Discussionmentioning

confidence: 99%

“…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).…”

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confidence: 99%

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

Roger

Wallis

Muller

et al. 2016

Antimicrob Agents Chemother

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“…This premise is supported by other studies that utilized higher dialysate or ultrafiltration rates with subsequent findings of higher rates of amikacin clearance. Roberts and colleagues reported data from five patients on CVVH, with average flow rates of 19.2 mL/min (1.2 L/h) and found a mean hemofiltration clearance rate of 16.4 mL/min [18]. Taken together, it appears that across studies, the overall dialytic dose may affect amikacin clearance.…”

Section: Discussionmentioning

confidence: 99%

“…Drug clearance for a particular medication may be affected by the mode of CRRT used, inter- and intra-patient variation in dialytic dose, and institutional variations in CRRT machines and filters. The majority of the reports on amikacin PK characteristics during CRRT were from a period of time where CRRT was performed with relatively lower dialysate or replacement fluid flow rates (0.6–1.2 L/h) compared to current CRRT prescriptions (2–4 L/h), or with hemofilters no longer used in clinical practice [15–18]. In addition, few of the reports provided the characteristics of the dialysis machine, the mode of CRRT, and filter details.…”

Section: Introductionmentioning

confidence: 99%

Amikacin Pharmacokinetics During Continuous Veno-Venous Hemodialysis

Lam

Bauer

2013

Infect Dis Ther

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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.

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“…There are some studies investigating the effects of CVVH on clearance of amikacin [12-14] but there is little published evidence describing the effect of CVVHDF. CVVH depends predominantly on convection alone while CVVHDF involves a combination of solute clearance by diffusion and convection, and is generally expected to have increased removal efficiency over CVVH [15].…”

Section: Introductionmentioning

confidence: 99%

An open prospective study of amikacin pharmacokinetics in critically ill patients during treatment with continuous venovenous haemodiafiltration

D’Arcy

Casey

Gowing

et al. 2012

BMC Pharmacol Toxicol

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BackgroundThe objectives of the current study were to determine amikacin pharmacokinetics in patients undergoing treatment with continuous venovenous haemodiafiltration (CVVHDF) in an Intensive Care Unit (ICU), and to determine whether peak and trough concentration data could be used to predict pharmacokinetic parameters. An open prospective study was undertaken, comprising five critically ill patients with sepsis requiring CVVHDF.MethodsPeak and trough plasma concentrations and multiple serum levels in a dosage interval were measured and the latter fitted to both a one- and two-compartment model. Blood and ultrafiltrate samples were collected and assayed for amikacin to calculate the pharmacokinetic parameters; total body clearance (TBC), elimination rate constant (k) and volume of distribution (Vd). The concentration of amikacin in ultrafiltrate was used to determine the clearance via CVVHDF. CVVHDF was performed at prescribed dialysate rates of 1-2l h-1 and ultrafiltration rate of 2l h-1. Blood was pumped at 200ml/min using a Gambro blood pump and Hospal AN69HF haemofilter. Amikacin dosing was according to routine clinical practice in the Intensive Care Unit.ResultsThe multi serum level study indicated that the one compartment model was adequate to characterize the pharmacokinetics in these patients suggesting that peak and trough plasma level data may be used to estimate individual patient pharmacokinetic parameters and to optimise individual patient dosing during treatment with CVVHDF. CVVHDF resulted in an amikacin k of 0.109+/−0.025 h, t1/2 of 6.74 +/− 1.69h, TBC of 3.39+/−0.817 h-1, and Vd of 31.4 +/− 3.27. The mean clearance due to CVVHDF of 2.86 l h-1 is similar to the creatinine clearance of 2.74 +/−0.4 lh-1. Amikacin was significantly cleared by CVVHDF, and its half life in patients on CVVHDF was approximately 2–3 times that reported in subjects without renal impairment and not undergoing haemodiafiltration for any reason.ConclusionsCVVHDF contributes significantly to total clearance of amikacin. The use of pharmacokinetic parameter estimates obtained from two steady state serum-drug concentrations (peak and trough) can be used to guide individualised dosing of critically ill patients treated with CVVHDF. This is considered a useful strategy in this patient cohort, particularly in avoiding the risk of underdosing.

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Amikacin Pharmacokinetics During Continuous Veno-Venous Hemofiltration

Cited by 16 publications

References 0 publications

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

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

Amikacin Pharmacokinetics During Continuous Veno-Venous Hemodialysis

An open prospective study of amikacin pharmacokinetics in critically ill patients during treatment with continuous venovenous haemodiafiltration

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