Pharmacokinetics of Caspofungin in Critically Ill Patients on Continuous Renal Replacement Therapy

Weiler, Stefan; Seger, Christoph; Pfisterer, Hartwig; Stienecke, Eva; Stippler, Florian; Welte, René; Joannidis, Michael; Griesmacher, Andrea; Bellmann, Romuald

doi:10.1128/aac.00335-13

Cited by 54 publications

(30 citation statements)

References 18 publications

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“…The AUC 0 -24 was low compared to the AUC 0 -24 of 98 mg · h/liter established in healthy volunteers (14)(15)(16), an AUC 0 -24 of 110 to 117 mg · h/liter found in non-critically ill patients (32,33), and an AUC 0 -24 of 89 to 116 mg · h/liter established in ICU patients (34,35). The volume of distribution in the peripheral compartment (V 2 ) was larger than (15,16,(32)(33)(34)(35). The half-life (t 1/2 ) was comparable to the t 1/2 in other ICU patients (34) and was longer than the t 1/2 in healthy volunteers (15,16).…”

Section: Discussionmentioning

confidence: 64%

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: Discussionmentioning

confidence: 64%

Low Caspofungin Exposure in Patients in Intensive Care Units

Elst

Veringa

Zijlstra

et al. 2017

Antimicrob Agents Chemother

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“…Small differences in pre-filter and post-filter concentrations suggest there might be some adsorption of caspofungin to the hemofilter membranes, but caspofungin PK parameters were not significantly influenced [105].…”

Section: Caspofunginmentioning

confidence: 94%

“…Single-dose and steady-state PK parameters of caspofungin were unchanged during CVVH in critically ill patients [105]. Small differences in pre-filter and post-filter concentrations suggest there might be some adsorption of caspofungin to the hemofilter membranes, but caspofungin PK parameters were not significantly influenced [105].…”

Section: Caspofunginmentioning

confidence: 98%

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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“…In CVVH and CVVHDF, the postfilter concentrations were corrected for postdilution. Calculations for pre-and postfilter clearance for all patients, as well as for sieving/saturation coefficient-based clearance for CVVHD (Cl HD ) and CVVH (Cl HF ), were performed using previously published formulae (8). Sieving coefficient-based clearance for CVVHDF (Cl HDF ) was calculated using a derived formula.…”

Section: Methodsmentioning

confidence: 99%

Doripenem Treatment during Continuous Renal Replacement Therapy

Vossen

Wenisch

Maier‐Salamon

et al. 2016

Antimicrob Agents Chemother

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dDoripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa. While the initial dosing recommendation for renally competent patients and patients undergoing continuous renal replacement therapy (cRRT) was 500 mg every 8 h (q8h), the dose for renally competent patients was updated to 1 g q8h in June 2012. There are no updated data for the dosing of patients on continuous renal replacement therapy. The original dosing regimen for cRRT patients was based on nonseptic patients, while newer publications chose comparatively low target concentrations for a carbapenem. Thus, there is an urgent need for updated recommendations for dosing during cRRT. In the trial presented here, we included 13 oliguric septic patients undergoing cRRT in an intensive care setting. Five patients each were treated with hemodiafiltration or hemodialysis, while three patients received hemofiltration treatment. All patients received 1 g doripenem every 8 h. Doripenem concentrations in the plasma and ultrafiltrate were measured over 48 h. The mean hemofilter clearance was 36.53 ml/min, and the mean volume of distribution was 59.26 liters. The steady-state trough levels were found at 8.5 mg/liter, with no considerable accumulation. Based on pharmacokinetic and pharmacodynamic considerations, we propose a regimen of 1 g q8h, which may be combined with a loading dose of 1.5 to 2 g for critically ill patients. (This study has been registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.)

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Pharmacokinetics of Caspofungin in Critically Ill Patients on Continuous Renal Replacement Therapy

Cited by 54 publications

References 18 publications

Low Caspofungin Exposure in Patients in Intensive Care Units

Low Caspofungin Exposure in Patients in Intensive Care Units

Impact of special patient populations on the pharmacokinetics of echinocandins

Doripenem Treatment during Continuous Renal Replacement Therapy

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