Pharmacokinetics of caspofungin in a critically ill patient with liver cirrhosis

Spriet, Isabel; Meersseman, Wouter; Annaert, Pieter; Hoon, Jan de; Willems, Ludo

doi:10.1007/s00228-011-1066-8

Cited by 22 publications

(20 citation statements)

References 5 publications

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“…The AUC 0 -24 was low in both patients, and the dose was increased to 50 mg, after which the AUC 0 -24 was adequate and liver enzymes remained stable. These results are in accordance with two case reports where 50 mg and 70 mg were given to patients with moderate hepatic dysfunction and where the exposure was similar to the exposure in healthy volunteers (39,40). These findings illustrate that liver drug metabolism may be underestimated in the presence of liver test abnormalities or evidence of cirrhosis (41).…”

Section: Discussionsupporting

confidence: 91%

“…Based on the results of that study, the authors state that the caspofungin maintenance dose should not be reduced in noncirrhotic ICU patients based on the Child-Pugh score if the classification is driven by hypoalbuminemia, as the decreased maintenance dose results in a significantly lower caspofungin exposure (42). Combined with the case reports and recent study (39,40,42), our findings suggest that patients with moderate hepatic dysfunction should perhaps initially receive a higher empirical maintenance dose, with close follow-up with therapeutic drug monitoring (TDM) and monitoring of liver enzymes. Further research in this patient group is needed to provide evidence for the development of new dosing recommendations.…”

Section: Discussionmentioning

confidence: 99%

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Low Caspofungin Exposure in Patients in Intensive Care Units

Elst

Veringa

Zijlstra

et al. 2017

Antimicrob Agents Chemother

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In critically ill patients, drug exposure may be influenced by altered drug distribution and clearance. Earlier studies showed that the variability in caspofungin exposure was high in intensive care unit (ICU) patients. The primary objective of this study was to determine if the standard dose of caspofungin resulted in adequate exposure in critically ill patients. A multicenter prospective study in ICU patients with (suspected) invasive candidiasis was conducted in the Netherlands from November 2013 to October 2015. Patients received standard caspofungin treatment, and the exposure was determined on day 3 of treatment. An area under the concentration-time curve from 0 to 24 h (AUC 0 -24 ) of 98 mg · h/liter was considered adequate exposure. In case of low exposure (i.e., Ͻ79 mg · h/liter, a Ն20% lower AUC 0 -24 ), the caspofungin dose was increased and the exposure reevaluated. Twenty patients were included in the study, of whom 5 had a positive blood culture. The median caspofungin AUC 0 -24 at day 3 was 78 mg · h/liter (interquartile range [IQR], 69 to 97 mg · h/liter). A low AUC 0 -24 (Ͻ79 mg · h/liter) was seen in 10 patients. The AUC 0 -24 was significantly and positively correlated with the caspofungin dose in mg/kg/day (P ϭ 0.011). The median AUC 0 -24 with a caspofungin dose of 1 mg/kg was estimated using a pharmacokinetic model and was 114.9 mg · h/liter (IQR, 103.2 to 143.5 mg · h/liter). In conclusion, the caspofungin exposure in ICU patients in this study was low compared with that in healthy volunteers and other (non)critically ill patients, most likely due to a larger volume of distribution. A weight-based dose regimen is probably more suitable for patients with substantially altered drug distribution. (This study has been registered at ClinicalTrials.gov under registration no. NCT01994096.)

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Low Caspofungin Exposure in Patients in Intensive Care Units

Elst

Veringa

Zijlstra

et al. 2017

Antimicrob Agents Chemother

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“…Renal function seems to be crucial in the prognosis of patients with severe AH [25]. Caspofungin is metabolized by the liver, but recent small studies have suggested that it is not toxic and is effective in patients with liver failure [26,27]. However, the ability of caspofungin to penetrate into the cerebrospinal fluid is poor, and cerebral aspergillosis was found in one quarter of our IA patients [28].…”

Section: Discussionmentioning

confidence: 91%

Invasive aspergillosis in patients with severe alcoholic hepatitis

Gustot

Maillart

Bocci

et al. 2014

Journal of Hepatology

121

134

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“…In contrast, case reports of patients with mild-to-moderate hepatic impairment treated with caspofungin 70 or 50 mg q.d. showed that dose reductions to 35 mg would possibly have lead to suboptimal exposure of caspofungin [91][92][93].…”

Section: Anidulafunginmentioning

confidence: 99%

Impact of special patient populations on the pharmacokinetics of echinocandins

Muilwijk¹,

Lempers²,

Burger³

et al. 2015

Expert Review of Anti-infective Therapy

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Echinocandins belong to the class of antifungal agents. Currently, three echinocandin drugs are licensed for intravenous treatment of invasive fungal infections: anidulafungin, caspofungin and micafungin. While their antifungal activity overlaps, there are substantial differences in pharmacokinetics (PK). Numerous factors may account for variability in PK of echinocandins including age (pediatrics vs adults), body surface area and body composition (normal weight vs obesity), disease status (e.g., critically ill and burn patients) and organ dysfunction (kidney and liver impairment). Subsequent effects of altered exposure might impact efficacy and safety. Knowledge of PK behavior is crucial in optimal clinical utilization of echinocandin in a specific patient or patient population. This review provides up-to-date information on PK data of anidulafungin, caspofungin and micafungin in special patient populations. Patient populations addressed are neonates, children and adolescents, obese patients, patients with hepatic or renal impairment, critically ill patients (including burn patients) and patients with hematological diseases.

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Pharmacokinetics of caspofungin in a critically ill patient with liver cirrhosis

Abstract: International audienc

Cited by 22 publications

References 5 publications

Low Caspofungin Exposure in Patients in Intensive Care Units

Low Caspofungin Exposure in Patients in Intensive Care Units

Invasive aspergillosis in patients with severe alcoholic hepatitis

Impact of special patient populations on the pharmacokinetics of echinocandins

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