Population Pharmacokinetics of Rezafungin in Patients with Fungal Infections

作者：Christopher M. Rubino, Shawn D. Flanagan · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2021 · DOI：10.1128/aac.00842-21 · 被引用次数：21 · 研究领域：Antifungal resistance and susceptibility、Fungal Biology and Applications、Fungal Infections and Studies

and Aspergillus, including subsets of resistant strains, and Pneumocystis jirovecii. The objective of this analysis was to develop a population pharmacokinetic (PK) model to characterize the disposition of rezafungin in plasma following intravenous (IV) administration in healthy volunteers and in patients with candidemia and/or invasive candidiasis. The population PK model was based on a previous model from phase 1 data; formal covariate analyses were conducted to identify any relationships between subject characteristics and rezafungin PK variability. A four-compartment model with linear elimination and zero-order drug input provided a robust fit to the pooled data. Several statistically significant relationships between subject descriptors (sex, infection status, serum albumin, and body surface area [BSA]) and rezafungin PK parameters were identified, but none were deemed clinically relevant. Previous dose justification analyses conducted using data from phase 1 subjects alone are expected to remain appropriate. The final model provided a precise and unbiased fit to the observed concentrations and can be used to reliably predict rezafungin PK in infected patients.