Pharmacokinetics of anidulafungin in critically ill patients in the intensive care unit with suspected or proven invasive fungal infections

Roger Brüggemann, Vera Middel-Baars, Dylan de Lange, Angela Colbers, Armand Girbes, Peter Pickkers, Noortje Swart

Abstract: 

Background: Anidulafungin is first line treatment candidemia or invasive candidiasis in critically ill patients. There is conflicting data on the pharmacokinetics of anidulafungin in ICU patients. Thus we set out to explore anidulafungin pharmacokinetics in ICU patients.

Material/methods: Adult ICU patients (from 3 hospitals) receiving anidulafungin as antifungal treatment were eligible. All patients received anidulafungin according to the label indication, constituting of a loading dose of 200 mg on day 1 followed by a maintenance dose of 100 mg from day 2 onward; there were no exclusion criteria for the study. Patients were evaluable when a full pharmacokinetic curve on day 3 was completed. In addition, daily trough samples and a PK curve on day 7 were taken. Samples were measured by a validated UPLC-fluorescence method. PK analysis was performed using a standard two-stage approach (Phoenix and SPSS). AUC on day 7 was compared to day 3 using a paired T-test on the log-transformed AUC values.

Results: 23 out of 36 patients (7 female, 16 male) were evaluable. Median (range) age and bodyweight were 66 (28-88) yr and 76 (50-115) kg. Pharmacokinetic sampling on day 3 (n=23) resulted in a median anidulafungin AUC0-24h of 72.1 (IQR 61.3-94.0) mg*h*L-1 , a median C24 of 2.2 (IQR 1.9-2.9) mg/L, a median Cmax of 5.3 (IQR4.1-6.0) mg/L, a median Vd of 46.0 (IQR 32.2-60.2) L and a median CL of 1.4 (IQR 1.1-1.6) L*h-1. Pharmacokinetic sampling on day 7 (n=13) resulted in a median AUC0-24h of 82.7 (IQR 73.0 – 129.5) mg*h*L-1 , a median Cmin of 2.8 (IQR 2.2 - 4.2 ) mg/L, a median Cmax of 5.9 (IQR 4.6 – 8.0) mg/L, a median Vd of 39.7 (IQR 32.2 – 54.4) L and a median CL of 1.2 (IQR 0.8 – 1.4) L*h-1 . The Geometric Mean Ratio for AUCday7 / AUCday3 was 1.13 (90% CI 1.03 – 1.25); visual inspection of daily trough concentrations did reveal a slight but not significant increase over time. We did not identify any significant covariates on anidulafungin pharmacokinetics (e.g. bodyweight, albumin, liver function). Anidulafungin was well tolerated.

Conclusions: Exposure of anidulafungin in ICU patients was lower compared to healthy volunteers or other patient populations. The exposure in the ICU patient population was comparable to previous reports on anidulafungin in ICU patients. The interindividual variability in pharmacokinetics was moderate whereas the intra-individual variability was limited. No significant covariates could be identified. Larger cohorts of patients or pooled data analyses are necessary to retrieve relevant covariates and to resolve the impact of the lower exposure.

2016

Poster: 

AttachmentSize
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abstract No: 

#3379

Full conference title: 

26th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 26th (2016)