期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 59, 期 7, 页码 3935-3943出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00102-15
关键词
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资金
- Pediatric Critical Care Scientist Development Program [5K12HD047349]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [1K23HD075891, 2K24HD058735]
- Duke-University of North Carolina Collaborative T32 Fellowship [1T32GM086330]
- Thrasher Research Fund
- NIGMS [1T32GM086330-01A1]
- Pediatric Critical Care and Trauma Scientist Development Program [5K12HD047349-10]
- U.S. Government [1R01HD057956-05, 1K24HD058735-05, U54 HD071600-01]
- U.S. Government (NICHD) [HHSN2752010000031]
- industry for neonatal and pediatric drug development
- Trius
- Cerexa Pharmaceuticals
- Abbott
- Theravance
- NIH [1R01-HD076676-01A1]
- National Center for Advancing Translational Sciences of the NIH [UL1TR001117]
- National Institute of Allergy and Infectious Disease [HHSN272201500006I, HHSN272201300017I]
- National Institute for Child Health and Human Development of the NIH [HHSN275201000003I]
- U.S. Food and Drug Administration [1U01FD004858-01]
- Biomedical Advanced Research and Development Authority (BARDA) [HHSO100201300009C]
Candida infections are a leading cause of infectious disease-related death in children supported by extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK); thus, standard fluconazole dosing may result in suboptimal drug exposures. The objective of our study was to determine the PK of fluconazole in children on ECMO. Forty children with 367 PK samples were included in the analysis. The PK data were analyzed using nonlinear mixed-effect modeling (NONMEM). A one-compartment model best described the data. Weight was included in the base model for clearance (CL) and volume of distribution (V). The final model included the effect of serum creatinine (SCR) level on CL and the effect of ECMO on V as follows: CL (in liters per hour) = 0.019 x weight x (SCR/0.4)(-0.29) x exp(eta(CL)) and V (in liters) = 0.93 x weight x 1.4(ECMO) x exp(eta(V)). The fluconazole V was increased in children supported by ECMO. Consequently, children on ECMO require a higher fluconazole loading dose for prophylaxis (12 mg/kg of body weight) and treatment (35 mg/kg) paired with standard maintenance doses to achieve exposures similar to those of children not on ECMO.
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