Electronic-Nomogram-Guided Micafungin Dosing Regimen in Critically Ill Patients: A Population Pharmacokinetic Study

Micafungin is recommended as a first-line antifungal agent for the treatment of invasive candidiasis. However, the optimal dosing regimen in critically ill patients remains uncertain due to marked interindividual pharmacokinetic variability. This study aimed to develop a population pharmacokinetic (popPK) model for micafungin and an electronic nomogram to support the selection of the optimal initial dosing regimen. A retrospective, monocentric pharmacokinetic study was conducted in a digestive ICU. PopPK modelling and covariate analysis were performed using Monolix.2024R1. Monte Carlo simulations (MCS) were subsequently used to build the e-nomogram. Overall, 404 micafungin plasma concentrations obtained from 100 patients were analysed, including 40% with cirrhosis and/or a history of liver transplantation. The concentration-time data were adequately described by a linear one-compartment model. The estimated PK parameters (between-subject variability) were 17.3 L (15%) for volume of distribution (Vd) and 0.85 L/h (25%) for clearance (Cl). Total body Weight (TBW) and total bilirubin were identified to influence Vd and/or Cl. External model evaluation showed acceptable predictive performance for both population and individual predictions. MCS suggested that the currently recommended regimen of 100 mg/day may be insufficient to achieve the PK/PD target for all Candida species when clinical breakpoint MIC values are considered. The resulting RShiny application provides clinicians with a practical decision support-toolfor selecting the best loading and maintenance doses according to TBW, BILI and the target pathogen, thereby maximising the probability of PK/PD target attainment.