Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenation.

Journal Article (Clinical Trial;Journal Article)

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 × weight × (SCR/0.4)(-0.29) × exp(ηCL) and V (in liters) = 0.93 × weight × 1.4(ECMO) × exp(ηV). 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.

Full Text

Duke Authors

Cited Authors

  • Watt, KM; Gonzalez, D; Benjamin, DK; Brouwer, KLR; Wade, KC; Capparelli, E; Barrett, J; Cohen-Wolkowiez, M

Published Date

  • July 2015

Published In

Volume / Issue

  • 59 / 7

Start / End Page

  • 3935 - 3943

PubMed ID

  • 25896706

Pubmed Central ID

  • PMC4468733

Electronic International Standard Serial Number (EISSN)

  • 1098-6596

Digital Object Identifier (DOI)

  • 10.1128/AAC.00102-15


  • eng

Conference Location

  • United States