Pharmacokinetics of Micafungin During Continuous Venovenous Hemofiltration

Study Overview
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Brief Summary
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Micafungin is a cyclic lipopeptide antifungal agent of the echinocandin class. Members of this class of antifungal agents are known to inhibit the synthesis of glucan polymers in fungal cell walls. The spectrum of activity of micafungin includes Candida (all species, including strains resistant to fluconazole), Aspergillus, and Pneumocystis. In intensive care patients continuous venovenous haemodiafiltration (CVVHDF) is a well-established extracorporal renal replacement therapy with a high clearance rate. Pharmacokinetic studies of antifungal agents in critically ill patients treated with CVVHDF are rare. Elimination of any given drug by renal replacement therapy is determined by several major factors which are membrane specific, due to physico-chemical properties of the drug and characteristics of the renal replacement technique used. Ten intensive-care patients with acute renal failure and suspected or proven candida infection are included into the study. 100 mg Micafungin will be infused over a period of sixty minutes via a central venous catheter, different from the venous catheter used for CVVHDF. Blood samples will be drawn on days 1 and 2 from the arterial and venous line of the extracorporeal circuit at 0, 2, 4, 6, 8 and 24h after starting the infusion. Plasma and ultrafiltration samples, collected from the outlet of the ultrafiltrate compartment of the hemofilter, will be taken at corresponding times. The following pharmacokinetic parameters will be determined: area under the curve (AUC), half-live (t1/2), maximum plasma concentration (Cmax) and elimination fraction.

Official Title
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Pharmacokinetics of Micafungin During Continuous Venovenous Hemofiltration

Conditions
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Candida Sepsis

Intervention / Treatment
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* Drug: Micafungin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19 to 70 years Suspected or proven candida infection requiring parenteral antifungal therapy. Continuous venovenous hemo(dia)filtration or Cica HD because of an acute renal failure. Exclusion Criteria: Known history of hypersensitivity to echinocandins. An expected survival of less than three days. Known alcohol dependency Known epilepsy Known pregnancy Known liver failure Soor oesophagitis

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Micafungin<br>Micafungin is administered per clinical need and the pharmacokinetic parameters are analyzed | Drug: Micafungin<br>* Measurement of PK<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemofiltration clearance of Micafungin | Haemofiltration clearance in ml/min measured by micafungin concentration gradient between hemodialyzer inlet and outlet port. | 49 hours |