Pharmacokinetic study of anidulafungin in ICU patients with intra-abdominal candidiasis.

Abstract

Background:

Only limited pharmacokinetic data are available for anidulafungin in ICU patients, especially in patients treated for severe intra-abdominal infection (IAI).

Methods:

This was a prospective multicentre observational study in ICU patients with suspected yeast IAI. All patients received an intravenous loading dose of 200 mg of anidulafungin, followed by 100 mg/day. Thirteen blood samples were drawn between day 1 and day 5 for pharmacokinetic analysis. Samples were analysed by an HPLC-tandem MS method. Demographics and SAPS2 and SOFA scores were recorded.

Results:

Fourteen patients with a median age (IQR) of 62 years (48-70) and with a mean BMI of 30.5 kg/m 2 were included from three centres; 57.1% were women. Their median (IQR) SAPS2 score was 54 (45-67) and their median (IQR) SOFA score was 8 (7-12). Six patients with community-acquired IAI and eight patients with nosocomial-acquired IAI were included. Twelve yeasts were isolated: six Candida albicans , two Candida glabrata , two Candida tropicalis , one Candida parapsilosis and one Candida krusei . Pharmacokinetic parameters were as follows [mean (% coefficient of variation)]: C max (mg/L) = 6.0 (29%); T max (h) = 1.6 (25.8%); C min (mg/L) = 3.2 (36.8%); AUC 0-24 (mg·h/L) = 88.9 (38.6%); t 1/2 (h) = 42.1 (68.2%); CL (L/h) = 1.2 (42.3%); and V (L) = 72.8 (87.8%). A two-compartment model best described the anidulafungin concentrations in the population pharmacokinetic study.

Conclusions:

The pharmacokinetic parameters of anidulafungin in critically ill ICU patients with complicated IAI are similar to those observed in the literature. However, an increased V and a longer t 1/2 were observed in this study. (EudraCT No. 2010-018695-25).

• Authors: H Dupont, L Massias, B Jung, N Ammenouche, P Montravers
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 72 Issue 5 Pg. 1429-1432 (05 01 2017) ISSN: 1460-2091 [Electronic] England
• PMID: 28088767 (Publication Type: Journal Article, Multicenter Study, Observational Study)
• Copyright: © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Antifungal Agents
• Echinocandins
• Anidulafungin

Topics

• Administration, Intravenous
• Aged
• Anidulafungin
• Antifungal Agents (administration & dosage, blood, pharmacokinetics, therapeutic use)
• Candida (drug effects, isolation & purification)
• Candida albicans (drug effects, isolation & purification)
• Candida glabrata (drug effects, isolation & purification)
• Candida tropicalis (drug effects, isolation & purification)
• Candidiasis (drug therapy, microbiology)
• Chromatography, High Pressure Liquid
• Critical Illness
• Echinocandins (administration & dosage, blood, pharmacokinetics, therapeutic use)
• Female
• Humans
• Intensive Care Units
• Intraabdominal Infections (drug therapy, microbiology)
• Male
• Microbial Sensitivity Tests
• Middle Aged
• Prospective Studies