Fluconazole Population Pharmacokinetics and Dosing for Prevention and Treatment of Invasive Candidiasis in Children Supported with Extracorporeal Membrane Oxygenation (original) (raw)

Antimicrobial Agents and Chemotherapy, 2015

Abstract

Candida infections are a leading cause of infectious disease-related death in children supported with extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK), thus standard fluconazole dosing may result in suboptimal drugexposure. 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. 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 creatinine (SCR) on CL, and ECMO on V, as follows: CL(L/h)=0.019*Weight*(SCR/0.4)(-0.29)*exp(ηCL) and V(L)=0.93*Weight*1.4(ECMO)*exp(ηV). Fluconazole V was increased in children supported with ECMO. Consequently, children on ECMO require a higher fluconazole loading dose for prophylaxis (12mg/kg) and treatment (35mg/kg) paired with standard maintenance doses to achieve exposures similar to children not on ECMO.

Edmund Capparelli hasn't uploaded this paper.

Let Edmund know you want this paper to be uploaded.

Ask for this paper to be uploaded.