Monte Carlo simulation optimization of fluconazole administration regimen for invasive candidiasis in patients with renal insufficiency
LIU Wei
ZHANG Yuping
YANG Ming
YU Yuanyuan
LIAO Wei
Abstract：Objective To optimize the fluconazole dosing regimen for patients with renal insufficiency suffering from invasive candidiasis and provide a reference for individualized medication in special populations.Methods Patients with renal insufficiency were grouped according to the glomerular filtration rate(GFR).Based on the pharmacokinetics/pharmacodynamics(PK/PD)model of fluconazole,the distribution of common clinical dosing regimens,pharmacokinetic(PK)parameters,and the minimum inhibitory concentration(MIC)of Candida was simulated by Monte Carlo simulation(MCS)using Crystal Ball software.The probability of target attainment(PTA)≥90%or the cumulative fraction of response(CFR)≥90%was used as the evaluation index.Results In the case where the MIC of the target Candida could be accurately obtained,when MIC≤1 mg/L,a dose of 100 mg/d(when MIC=1 mg/L,the dose for patients with mild renal insufficiency needed to be increased to 200 mg/d)could meet the requirement of PTA≥90%;when MIC=2 mg/L,for patients with mild or moderate renal insufficiency,the maintenance dose recommended in the package insert(for patients with severe renal insufficiency,a dose of 100 mg/d was required)could meet the requirement of PTA≥90%;when MIC=4 mg/L,only a dose of 200 mg/d for patients with severe renal insufficiency could meet the requirement of PTA≥90%;and when MIC>4 mg/L,the dose recommended in the package insert could not meet the requirement of PTA≥90%.In the case where only the strain could be identified but the accurate drug susceptibility results could not be obtained,a dose of 200 mg/d for patients with mild renal insufficiency could meet the requirement of CFR≥90%for the target Candida;while patients with moderate or severe renal insufficiency required a dose of 100 mg/d to meet the requirement of CFR≥90%.Conclusion For patients with renal insufficiency using fluconazole,factors such as the Candida strain,MIC value,and the degree of renal function impairment should be comprehensively considered to achieve individualized dosing.
Keywords：fluconazoleinvasive candidiasisMonte Carlo simulationpharmacokinetics/pharmacodynamicsrenal insufficiency
Publication Date：2025-12-28
Online Publishing Date：2026-01-06(First online date of this platform, not the publication date of the document)
Pages：5( 576-580 )