Pharmacokinetic, Pharmacokinetic/Pharmacodynamic, and Safety Investigations of Cefiderocol in Chinese Healthy Subjects

• DOI: 10.1007/s12325-025-03147-1
• Publication Date: 2025-03-13T08:06:31Z
• Authors: Chuhan Zhang; Shuyan Yu; Size Li; Xiaojie Wu; Qiong Wei; Jinjie He; Guoying Cao; Haijing Yang; Jingjing Wang; Kohei Fujitani; Takayuki Katsube; Jing Zhang; Honghong Dou
• Keywords: Pharmacodynamics

We aim to evaluate the safety and pharmacokinetic (PK) properties of cefiderocol in Chinese participants, following single subsequent multiple administrations 2 g q8h with 3-h intravenous infusion, predict its efficacy for treatment Gram-negative bacilli (GNB) infection based on PK/pharmacodynamic (PD) analysis. This was an open-label, single-center, single- multiple-dose phase I study, conducted from September 2022 October 2022, 12 eligible healthy adults (6 men 6 women). The PK profiles were described by noncompartmental analysis a two-compartment model using WinNonlin (v.8.1). Monte Carlo simulations (MCS) performed R (v.4.3.1) obtain probability target attainment (PTA) as well cumulative fraction response (CFR), previously published data susceptibility studies China. Both doses tolerated subjects, no severe treatment-emergent adverse events occurred. maximum plasma concentration observed approximately 3 h after administration half-life about 2.6 h, accumulation dosing. It is worth noting that, profiles, including CL, V1, Cmax, Ctrough, AUC0–τ, consistent those other populations, e.g., Caucasian. PK/PD MCS suggested that standard dosage regimen would achieve satisfactory PTA CFR (exceeding 90%) pathogens MICs up 4 μg/mL, proposed fT>MIC 75.0%. Consistently, more than 90% reached Enterobacterales, P. aeruginosa, Acinetobacter spp. μg/mL at their respective 73.3%, 72.2%, 88.1% targets, exceeding 95%. Especially S. maltophilia, both nearly 100% high 8 μg/mL. Cefiderocol participants via which expected treating GNB infections China, although further optimization might still be required. To our knowledge, this first study describe microbiological ChiCTR2300076607.