Pharmacokinetics of Voriconazole in Peritoneal Fluid of Critically Ill Patients

Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, draw...

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Published in:Antimicrobial agents and chemotherapy 2023-05, Vol.67 (5), p.e0172122-e0172122
Main Authors: Lin, Xiao-Bin, Hu, Xiao-Guang, Tang, Zhao-Xia, Guo, Peng-Hao, Liu, Xiao-Man, Liang, Tao, Xia, Yan-Zhe, Lui, Ka Yin, Chen, Pan, Tang, Ke-Jing, Chen, Xiao, Cai, Chang-Jie
Format: Article
Language:English
Subjects:
Antifungal Agents - pharmacokinetics
Antimicrobial Chemotherapy
Ascitic Fluid
Candida glabrata
Critical Illness
Humans
Microbial Sensitivity Tests
Pharmacology
Prospective Studies
Voriconazole - pharmacokinetics
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Summary:Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, drawn after single (first dose on day 1) and multiple (steady-state) doses, displayed a slower rise and lower fluctuation of VRC concentrations in peritoneal fluid than in plasma. Good but variable penetration of VRC into the peritoneal cavity was observed, and the median (range) peritoneal fluid/plasma ratios of the area under the concentration-time curve (AUC) were 0.54 (0.34 to 0.73) and 0.67 (0.63 to 0.94) for single and multiple doses, respectively. Approximately 81% (13/16) of the VRC steady-state trough concentrations ( ) in plasma were within the therapeutic range (1 to 5.5 μg/mL), and the corresponding (median [range]) in peritoneal fluid was 2.12 (1.39 to 3.72) μg/mL. Based on the recent 3-year (2019 to 2021) surveillance of the antifungal susceptibilities for species isolated from peritoneal fluid in our center, the aforementioned 13 in peritoneal fluid exceeded the MIC of C. albicans, C. glabrata, and C. parapsilosis (0.06, 1.00, and 0.25 μg/mL, respectively), which supported VRC as a reasonable choice for initial empirical therapies against intraabdominal candidiasis caused by these three species, prior to the receipt of susceptibility testing results.
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.01721-22