Pharmacokinetics of Micafungin in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis With High Cutoff Membranes. 2019

Teresa Tenorio-Cañamás, and Santiago Grau, and Sonia Luque, and Jesús Fortún, and Fernando Liaño, and Jason A Roberts
Department of Nephrology, Hospital Universitario Ramón y Cajal, Madrid.

An optimal antifungal therapy for invasive candidiasis in critically ill patients is essential to reduce the high mortality rates. Acute kidney injury is common, and continuous renal replacement therapies are frequently used. Previous studies have demonstrated a lack of effect from different continuous renal replacement techniques on micafungin clearance. However, the use of high cutoff pore size membranes could potentially allow for the loss of albumin and alter micafungin pharmacokinetics. The objective was to explore the pharmacokinetics of micafungin in critically ill patients undergoing continuous venovenous high cutoff membrane hemodialysis (CVVHD-HCO). Prospective observational study performed in critically ill patients treated with 100 mg/d of micafungin and undergoing CVVHD-HCO. CVVHD-HCO sessions were performed using Prisma-Flex monitors and dialyzers with a membrane of polyarylethersulfone of 1.1-m surface area and 45-kDa pore size. Blood samples were collected from arterial prefilter, venous postfilter, and the drainage line ports at 0 (predose), 1, 4, 12, 24 hours after dose, and micafungin concentrations were determined using HPLC-UV. Nine patients (55.6% male; age: 28-80 years) were included. Median (range) of micafungin concentrations in the effluent were <0.2 (<0.2-0.4) mg/L at low (predose) and 0.4 (<0.2-0.7) mg/L at high (1 h) concentrations. The extraction ratio was <12% at each time point. A 2-compartment model best described the time course of plasma concentrations, and body weight was the only covariate that improved the model. This is the first study demonstrating that CVVHD-HCO does not alter the pharmacokinetics of micafungin, and that standard doses of this antifungal can be used.

UI MeSH Term Description Entries
D007362 Intensive Care Units Hospital units providing continuous surveillance and care to acutely ill patients. ICU Intensive Care Units,Intensive Care Unit,Unit, Intensive Care
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077551 Micafungin A cyclic lipo-hexapeptide echinocandin antifungal agent that is used for the treatment and prevention of CANDIDIASIS. FK 463,FK-463,FK463,Micafungin Sodium,Mycamine
D000079664 Continuous Renal Replacement Therapy Procedures with continuous blood purification (e.g., dialysis, filtration or perfusion) via vascular access designed to mimic kidney function in kidney diseases (e.g., ACUTE RENAL FAILURE and poisoning). CAVHD,CRRT Technique,CVVH Technique,CVVHD,CVVHDF,Continuous Arterio-Venous Ultrafiltration,Continuous RRT,Continuous Renal Replacement Procedure,Continuous Veno-Venous Hemodiafiltration,Continuous Veno-Venous Hemodialysis,Continuous Veno-Venous Hemofiltration,Continuous Venovenous Hemodiafiltration,Continuous Venovenous Hemodialysis,Continuous Venovenous Hemofiltration,Hemofiltration, Continuous Arteriovenous,SCUF Technique,Slow Continuous Ultrafiltration,Arterio-Venous Ultrafiltration, Continuous,Arteriovenous Hemofiltration, Continuous,CVVH Techniques,Continuous Arterio Venous Ultrafiltration,Continuous Arterio-Venous Ultrafiltrations,Continuous Arteriovenous Hemofiltration,Continuous Arteriovenous Hemofiltrations,Continuous RRTs,Continuous Veno Venous Hemodiafiltration,Continuous Veno Venous Hemodialysis,Continuous Veno Venous Hemofiltration,Continuous Veno-Venous Hemodiafiltrations,Continuous Veno-Venous Hemodialyses,Continuous Veno-Venous Hemofiltrations,Continuous Venovenous Hemodiafiltrations,Continuous Venovenous Hemodialyses,Continuous Venovenous Hemofiltrations,Hemodiafiltration, Continuous Veno-Venous,Hemodiafiltration, Continuous Venovenous,Hemodialysis, Continuous Veno-Venous,Hemodialysis, Continuous Venovenous,Hemofiltration, Continuous Veno-Venous,Hemofiltration, Continuous Venovenous,RRT, Continuous,SCUF Techniques,Slow Continuous Ultrafiltrations,Ultrafiltration, Continuous Arterio-Venous,Veno-Venous Hemodiafiltration, Continuous,Veno-Venous Hemodialyses, Continuous,Veno-Venous Hemodialysis, Continuous,Veno-Venous Hemofiltration, Continuous,Venovenous Hemodiafiltration, Continuous,Venovenous Hemodialysis, Continuous,Venovenous Hemofiltration, Continuous
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly

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