Pharmacokinetics of Micafungin in Patients of Intensive Care Units (MI-K)

Invasive fungal infections (IFIs) are a frequent cause of morbidity and mortality in high-risk patients, such as immunocompromised patients. Candida is currently the predominant fungal pathogen in these patient populations and is associated with significant morbidity and a high mortality.

Micafungin (MCF) is a semisynthetic compound belonging to the new class of antifungal agents, the echinocandin lipopeptides, that has potent in vitro and experimental in vivo activity against a variety of pathogenic Candida species and Aspergillus species. Its applied indications are so the treatment and/or the prophylaxis of Candida and Aspergillus infections. MCF is currently licensed for the treatment of candidiasis at doses of either 100 or 150 mg a day.

The efficacy of MCF is linked to the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC0-24/ MIC ratio).

On one hand:

- It was demonstrated that 98% of invasive candidiasis patients with a MCF AUC/MIC ratio between 3 and 12 achieve microbiological clearance, as opposed to only 85% of those with an AUC/MIC ratio < 3. In the case of infections by Candida parapsilosis, which exhibits drug MICs that are 50- to100-fold higher, 100% of patients with an AUC/MIC ratio >285 achieve microbiological clearance, as opposed to 82% of those below that exposure level.(1)

On the other hand:

• It is well known that patients of intensive care units (ICU) are characterized by particular pharmacokinetic parameters with higher apparent volume of distribution (VC/F) and/or higher apparent systemic clearance (CL/F). In a population of healthy volunteers, it was observed that CL/F of MCF presents a high interpatient variability.(2)
• Whether most ICUs patients achieve optimal AUC/MIC ratio thresholds at standard doses has not been investigated so far. In particular, lower AUCs might be reached in patients having the highest VC/F values. Such patients would then be at risk of therapy failure and would benefit from individualized-dosing strategies.

In this context, the study of the pharmacokinetics of MCF in critically ill patients seems to be necessary.

Study Overview

• Status: Completed
• Conditions: Invasive Candidiasis
• Intervention / Treatment: Other: micafungin

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • CHU de Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Critically ill patients hospitalized in an ICU, with suspected or proven invasive fungal infections, for whom the decision has been made to start a treatment based on MCF.
• Age > 18 years.
• Patients willing to give their written informed consent for their participation to the study.
• Patients affiliated to the French social security system or equivalent.

Exclusion Criteria:

• Patient for whom a treatment based on MCF has already been started
• Patient who have benefited from bone marrow transplantation
• Age < 18 years
• Patient under legal protection
• Patient deprived of liberty
• Pregnant or breast-feeding woman or woman of childbearing potential without efficient contraception (based on declaration)
• Patient with any altered mental status or any psychiatric condition that would interfere with the understanding of the study
• Patient enrolled in another clinical trial testing drugs or therapeutic strategies (including the so-called "exclusion period")

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pharmacokinetics of micafungin	Other: micafungin; This is a pharmacokinetic study where a total number of 14 blood samples will be drawn per patient. Clinical and biological data will be concomitantly collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe micafungin concentrations over time,	The evaluation of the PK model performance will be based on its ability: To describe micafungin concentrations over time,; To explain the sources of inter-individual PK variability. It will be done by the calculation of the bias between concentrations predicted using the model and observed concentrations.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To estimate the proportion of patients hospitalized in an ICU achieving the target AUC or AUC/MIC when receiving the recommended regimen	The estimation of the proportion of patients hospitalized in an ICU achieving the target AUC or AUC/MIC when receiving the recommended regimen will be based on the determination of exposure indices (AUC) and mycological characteristics (fungus and its MIC)	3 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Limoges

Publications and helpful links

General Publications

• Berrah R, Saint-Marcoux F, Monchaud C, Cointault O, Conseil M, Jaber S, Jung B, Woillard JB. From AUC/MIC to AUCss and Cmin: Optimizing Micafungin Therapy in the Critically Ill through Model-Informed Precision Dosing. AAPS J. 2025 Nov 11;28(1):18. doi: 10.1208/s12248-025-01173-z.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: June 13, 2014
• First Submitted That Met QC Criteria: June 16, 2014
• First Posted (Estimated): June 17, 2014

Study Record Updates

• Last Update Posted (Estimated): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Invasive Fungal Infections; Infections; Bacterial Infections and Mycoses; Mycoses; Candidiasis; Candidiasis, Invasive; Peptides; Amino Acids, Peptides, and Proteins; Lipids; Peptides, Cyclic; Lipopeptides; Echinocandins; Micafungin
• Other Study ID Numbers: I13025