title: Limited-sampling strategies for anidulafungin in critically ill patients.
abstract: Efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Determination of the anidulafungin AUC along with MIC values can therefore be useful. Since obtaining a full concentration-time curve to determine an AUC is not always feasible or appropriate, limited-sampling strategies may be useful in adequately estimating exposure. The objective of this study was to develop a model to predict the individual anidulafungin exposure in critically ill patients using limited-sampling strategies. Pharmacokinetic data were derived from 20 critically ill patients with invasive candidiasis treated with anidulafungin. These data were used to develop a two-compartment model in MW\Pharm using an iterative 2-stage Bayesian procedure. Limited-sampling strategies were subsequently investigated using two methods, a Bayesian analysis and a linear regression analysis. The best possible strategies for these two methods were evaluated by a Bland-Altman analysis for correlation of the predicted and observed AUC from 0 to 24 h (AUC0-24) values. Anidulafungin exposure can be adequately estimated with the concentration from a single sample drawn 12 h after the start of the infusion either by linear regression (R2=0.99; bias, 0.05%; root mean square error [RMSE], 3%) or using a population pharmacokinetic model (R2=0.89; bias, -0.1%; RMSE, 9%) in critically ill patients and also in less severely ill patients, as reflected by healthy volunteers. Limited sampling can be advantageous for future studies evaluating the pharmacokinetics and pharmacodynamics of anidulafungin and for therapeutic drug monitoring in selected patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01047267.).
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: Marjolijn J P
authors.initials: MJ
authors.lastname: van Wanrooy
authors.affiliation: University of Groningen, Department of Pharmacy, Section Pharmacokinetics, Toxicology and Targeting, Groningen, The Netherlands.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Proost
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, The Netherlands.
authors.forename: Michael G G
authors.initials: MG
authors.lastname: Rodgers
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, The Netherlands.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Zijlstra
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: Donald R A
authors.initials: DR
authors.lastname: Uges
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands University of Groningen, Department of Pharmacy, Section Pharmacotherapy and Pharmaceutical Care, Groningen, The Netherlands.
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.affiliation: University of Groningen, University Medical Center Groningen, Departments of Internal Medicine and Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands.
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands j.w.c.alffenaar@umcg.nl.
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000328:Adult; D000368:Aged; D000077612:Anidulafungin; D001499:Bayes Theorem; D058365:Candidiasis, Invasive / Q000188:drug therapy; D016638:Critical Illness; D054714:Echinocandins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D054714:Echinocandins; D000077612:Anidulafungin