Τίτλος:
Population pharmacokinetics of micafungin over repeated doses in critically ill patients: a need for a loading dose?
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objectives: To study the population pharmacokinetics of micafungin in critically ill patients, evaluate and optimize dosage regimens. Methods: An HPLC–fluorescence bioassay for micafungin was developed, fully validated and applied to a pharmacokinetic study conducted in 14 ICU patients. Dense blood sampling was performed from days 1 to 7. A population pharmacokinetic model accounting for interindividual (IIV) and interoccasion variability (IOV) of the PK parameters was developed. Simulations were performed to estimate the probability of target attainment (PTA) for several dosing regimens. Key findings: A two-compartment pharmacokinetic model best described the data, with population clearance CL = 1.31 L/h and central volume V1 = 14.2 L. The relatively high IOV observed (45% for CL, 27% for V1) sets limits for the dose individualization in this population. The low PTA on the first day of treatment suggests the need of a loading dose. PTA and CFR estimates show that the current micafungin dosage may be insufficient for the treatment of borderline susceptible Candida strains. Conclusions: A loading dose of up to 300 mg of micafungin is needed for the treatment of invasive candidiasis in ICU patients while a maintenance dose of up to 200 mg can be considered in empirical antifungal treatment. © 2020 Royal Pharmaceutical Society
Συγγραφείς:
Kapralos, I.
Mainas, E.
Neroutsos, E.
Apostolidi, S.
Siopi, M.
Apostolopoulou, O.
Dimopoulos, G.
Sambatakou, H.
Valsami, G.
Meletiadis, J.
Dokoumetzidis, A.
Περιοδικό:
The Journal of pharmacy and pharmacology
Εκδότης:
Wiley-Blackwell Publishing Ltd
Λέξεις-κλειδιά:
micafungin; antifungal agent; micafungin, adult; aged; Article; blood sampling; Candida albicans; Candida glabrata; Candida parapsilosis; central volume of distribution; clinical article; compartment model; critically ill patient; drug clearance; drug dose regimen; female; fluorescence analysis; high performance liquid chromatography; human; intercompartmental clearance; loading drug dose; male; Monte Carlo method; peripheral volume of distribution; pharmacokinetic parameters; repeated drug dose; residual unexplained variability; biological model; blood; candidiasis; computer simulation; critical illness; dose calculation; drug monitoring; fluorometry; intensive care unit; intravenous drug administration; microbiology; middle aged; predictive value; reproducibility; very elderly, Adult; Aged; Aged, 80 and over; Antifungal Agents; Candidiasis; Chromatography, High Pressure Liquid; Computer Simulation; Critical Illness; Drug Dosage Calculations; Drug Monitoring; Female; Fluorometry; Humans; Infusions, Intravenous; Intensive Care Units; Male; Micafungin; Middle Aged; Models, Biological; Predictive Value of Tests; Reproducibility of Results
