Comparative population plasma and tissue pharmacokinetics of micafungin in critically ill patients with severe burn injuries and patients with complicated intra-abdominal infection

Garcia-De-Lorenzo, A., Luque, S., Grau, S., Agrifoglio, A., Cachafeiro, L., Herrero, E., Asensio, M. J., Sanchez, S. M. and Roberts, J. A. (2016) Comparative population plasma and tissue pharmacokinetics of micafungin in critically ill patients with severe burn injuries and patients with complicated intra-abdominal infection. Antimicrobial Agents and Chemotherapy, 60 10: 5914-5921. doi:10.1128/AAC.00727-16

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Author Garcia-De-Lorenzo, A.
Luque, S.
Grau, S.
Agrifoglio, A.
Cachafeiro, L.
Herrero, E.
Asensio, M. J.
Sanchez, S. M.
Roberts, J. A.
Title Comparative population plasma and tissue pharmacokinetics of micafungin in critically ill patients with severe burn injuries and patients with complicated intra-abdominal infection
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 1098-6596
0066-4804
Publication date 2016-10-01
Sub-type Article (original research)
DOI 10.1128/AAC.00727-16
Open Access Status File (Publisher version)
Volume 60
Issue 10
Start page 5914
End page 5921
Total pages 8
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2017
Language eng
Formatted abstract
Severely burned patients have altered drug pharmacokinetics (PKs), but it is unclear how different they are from those in other critically ill patient groups. The aim of the present study was to compare the population pharmacokinetics of micafungin in the plasma and burn eschar of severely burned patients with those of micafungin in the plasma and peritoneal fluid of postsurgical critically ill patients with intra-abdominal infection. Fifteen burn patients were compared with 10 patients with intra-abdominal infection; all patients were treated with 100 to 150 mg/day of micafungin. Micafungin concentrations in serial blood, peritoneal fluid, and burn tissue samples were determined and were subjected to a population pharmacokinetic analysis. The probability of target attainment was calculated using area under the concentration-time curve from 0 to 24 h/MIC cutoffs of 285 for Candida parapsilosis and 3,000 for non-parapsilosis Candida spp. by Monte Carlo simulations. Twenty-five patients (18 males; median age, 50 years; age range, 38 to 67 years; median total body surface area burned, 50%; range of total body surface area burned, 35 to 65%) were included. A three-compartment model described the data, and only the rate constant for the drug distribution from the tissue fluid to the central compartment was statistically significantly different between the burn and intra-abdominal infection patients (0.47 ± 0.47 versus 0.15 ± 0.06 h-1, respectively; P < 0.05). Most patients would achieve plasma PK/pharmacodynamic (PD) targets of 90% for non-parapsilosis Candida spp. and C. parapsilosis with MICs of 0.008 and 0.064 mg/liter, respectively, for doses of 100 mg daily and 150 mg daily. The PKs of micafungin were not significantly different between burn patients and intra-abdominal infection patients. After the first dose, micafungin at 100 mg/day achieved the PK/PD targets in plasma for MIC values of ≤0.008 mg/liter and ≤0.064 mg/liter for non-parapsilosis Candida spp. and Candida parapsilosis species, respectively.
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