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RESEARCH PRODUCT

Pharmacokinetics of anidulafungin during albumin dialysis

subject

description

In the ICU setting, current guidelines recommend echi-nocandins as the first-line treatment for invasive candi-diasis [1]. Albumin dialysis (AD) has been used in theICU as supportive therapy for hepatic failure, but thistechnique can significantly enhance drug elimination [2].We prescribed anidulafungin for suspected invasivecandidiasis in a patient with severe liver failure treatedwith AD and measured the plasma concentrations of thedrug using high-performance liquid chromatography.This study (GEF-ANI-2010-02) was approved by thelocal ethics committee (INCLIVA, Institute of Research,Valencia, Spain) and written informed consent wasobtained from the patient’s next of kin. An adult patientwas admitted to our ICU with acute liver failure aftermajor hepatectomy for metastasis. The patient was givenanidulafungin (200 mg loading dose on day 1, followedby 100 mg daily) for suspected invasive candidiasis. Onthe fourth day, the patient developed encephalopathyand complained of increasing pruritus. AD using theMolecular Adsorbent Recirculating System (GambroHospal AG, Zurich, Switzerland) was therefore startedwhile waiting for liver function to improve. Arterialblood, urine, and dialysate samples were collected atdifferent times after the first AD session was initiated:before starting the fourth anidulafungin infusion and at0.5, 1, 1.5, 2, 4, 6, and 8 hours after starting the infusion.The last samples (8 hours) were obtained when AD wasfinished. Anidulafungin was well tolerated withoutrelevant adverse effects.The following pharmacokinetic parameters were calcu-lated: area under the concentration curve from 0 to 8 hoursusing the linear trapezoidal rule, and the eliminationhalf-life with noncompartmental analysis. The values forthe peak plasma concentration, the through plasma con-centration, and the time to reach the peak plasma concen-tration were calculated from the observed values (Figure 1).Plasma, urine, and dialysate samples were analysed.The limit of quantification was 0.5 mg/l. No anidulafun-gin levels were measurable in the ultradiafiltrate andurine samples. The peak plasma concentration with the100 mg dose on day 4 was 9.45 mg/l (Figure 1).Only two reports regarding the use of antifungals duringAD were found in the literature, demonstrating that theinfluence of this technique on drug elimination appeared tobe negligible [3,4]. We report the first pharmacokineticstudy of anidulafungin during AD. Although the mainlimitation of our study is the enrolment of only one patientand the sampling being no more than 8 hours, AD appearsto have little influence on the pharmacokinetics of anidula-fungin and an adjustment of the drug dose is probably notrequired. However, further research is needed to confirmour findings.