In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-11-28)
Abstract:
We investigated covariates of pharmacokinetics of micafungin in critically ill patients. After application of micafungin, plasma samples were collected. Non-linear mixed effects modelling (NONMEM 7.3) was used to develop the pharmacokinetic model. Using this model, the adequacy of a fixed 100 mg dosing regimen was evaluated in the study cohort. A two-compartment model with linear elimination was found to describe the obtained data. SOFA score was identified as a significant covariate on both clearance and central volume of distribution, respectively. Patients in highly critical condition, represented by a SOFA above 10 showed a 30.8% lower central volume of distribution than the less critically ill patients. For patients with bilirubin levels above 4 mg/dl, clearance was decreased by 21.1%. Renal replacement therapy (RRT) did not influence micafungin clearance or the volumes of distribution. In a posthoc evaluation of the modeled population, 100 mg micafungin was suitable when assessing the PKPD targets (AUC/MIC) for C . albicans and C . glabrata , with insufficient target attainment for C . parapsilosis . Micafungin pharmacokinetics appear not to be influenced by the status of RRT. A dose of 100 mg micafungin is suitable for infections with C . albicans and C . glabrata in critically ill patients.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-019-53093-6
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2019
detail.hit.zdb_id:
2615211-3
