Abstract
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.
Highlights
The 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
The objectives of the study were: a) to carry out a prospective study of patients treated with amikacin and CVVHDF, and to determine amikacin pharmacokinetic parameters including an estimate of clearance due to CVVHDF b) to determine whether a 1-compartment model or a 2-compartment model better fitted multiple serum concentration data over the course of one dosage interval in patients on CVVHDF. c) to determine whether peak and trough data alone would be adequate to calculate pharmacokinetic parameters and subsequent dose recommendations, as this data is obtained during routine therapeutic drug monitoring (TDM) practice
Patient demographics Three men and two women treated with amikacin during CVVHDF therapy, ages 57–70 were enrolled in the study
Summary
The 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. Aminoglycoside antibiotics are used to treat serious infections caused by gram negative microorganisms in intensive care unit (ICU) patients They are an increasingly popular choice for both empiric and directed therapy as they are less likely to engender resistance than quinolones [1] and have a lesser incidence of promoting Clostridium difficile infection than other antibiotics [2]. Its dosage regimens must be adjusted in severe renal insufficiency to prevent accumulation of the drug to toxic levels and the associated risk of oto- and nephrotoxicity. This drug’s hydrophilicity and low molecular weight make it likely to be cleared by CVVHDF and pharmacokinetic studies during CVVHDF are required to optimise dosing regimens and obtain therapeutic concentrations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
