Severely burned patients have altered drug pharmacokinetics but it is unclear how different it is from other critically ill patient groups. The aim was to compare the population pharmacokinetics of micafungin in plasma and burn eschar in severely burned patients with micafungin in plasma and peritoneal fluid of postsurgical critically-ill patients with intra-abdominal infection.
Fifteen burned patients were compared with 10 patients with intra-abdominal infection, all treated with 100-150mg/day of micafungin. Micafungin concentrations were determined in serial blood, peritoneal fluid and burn tissue samples and were subjected to a population pharmacokinetic analysis. The probability of target attainment was calculated using AUC0-24/MIC cutoffs: 285 (C. parapsilosis) and 3000 (non-parapsilosis Candida spp.), by Montecarlo simulations.
Twenty-five patients included (18 male, median (range) 50 (38-67) years, total body surface area burned 50% (35-65) in burns). A three compartment model described the data and only the rate constant for drug distribution from the tissue fluid to central compartment was statistically different between burns and intra-abdominal infection patients (0.47 (0.47) vs 0.15 (0.06) h(-1); p<0.05), respectively. Most patients would achieve plasma PK/PD targets for 90% of non-parapsilosis Candida spp. and C. parapsilosis with MICs of 0.008 and 0.064 for 100mg daily and 150mg daily doses, respectively.
The PK of micafungin is not significantly different between burns in intra-abdominal infection patients. After the first dose, micafungin 100 mg/day achieves PK/PD targets in plasma for MICs values ≤ 0.008 mg/L and ≤ 0.064 mg/L for non-parapsilosis Candida spp. and Candida parapsilosis species, respectively.