In addition, few of the reports provided the characteristics of the dialysis machine, the mode of CRRT, and filter details. Lastly, only one report describes the PK characteristics of amikacin in patients undergoing continuous veno-venous hemodialysis (CVVHD) [16]. There are several reports of amikacin PK with novel CRRT parameters; however, they comprise fewer than 30 cases in total. Furthermore, some novel reports of amikacin PK characteristics involved five or fewer patients in their analysis [21, 22] and one report focused on patients with burn injury [20], which may have confounding PK implications. Given the paucity of data and the continued need for broad-spectrum antibiotics targeting Gram-negative pathogens
in an era of newer CRRT machines and filters with drastically higher flow rates,
the PK characteristics of amikacin warrant further investigation. As such, we performed a prospective observational selleck inhibitor study of patients ZD1839 in vivo who received amikacin therapy while on CVVHD to further characterize the PK parameters of the medication. Materials and Methods This was a prospective observational study of a convenient sample of patients admitted to a medical ICU of a tertiary care academic medical center, who received amikacin therapy while on CVVHD. Patient characteristics, amikacin dosing, and CVVHD parameters, including machine, filter, effluent, and dialysate flow rates, were collected from an intensive care database that was approved by the Cleveland Clinic Institutional Review Board (IRB). The database was approved by the local IRB as part of a registry for the evaluation of intensive care pharmacotherapy-related outcomes. The current study was performed by querying the existing data within the registry with no additional information
collected through chart review or patient contact. A waiver of informed consent was granted by the local IRB. The decision to administer amikacin and the prescribed dose/frequency were determined by the primary ICU service, and not prescribed by the study protocol. Patients with at least two amikacin serum sample concentrations measured after the first dose of amikacin were included in the study. Serum amikacin concentration Erastin measurements were drawn as part of routine patient monitoring and levels were generally determined more than 8 h apart. Amikacin levels were measured by our local institutional laboratory using the Advia® 1200 system (Siemens Medical Solutions, Malvern, PA, United States) chemistry analyzer with an enzyme immunoassay technique. The assay measures total amikacin level and has a quantification range of 2.5–50 μg/mL, with a detection limit of 1 μg/mL and a coefficient of variation of approximately 10%. First-order pharmacokinetics with a single compartment were assumed and estimations of the peak concentration (C max), volume of distribution (V d), elimination constant (K el), clearance (Cl), and terminal half-life (t ½) were performed.