Pharmacokinetics, safety, tolerability and fluorescence imaging of nizaracianine triflutate administered in three divided doses to healthy volunteers

Aim Fluorescence‐guided surgery enhances intraoperative visualization of anatomical structures. Nizaracianine is a near‐infrared fluorescent agent that is exclusively renally cleared in animal models. It enables real‐time ureteral imaging and identification, potentially reduces risk of injury and facilitates assessment before surgical closure. While a single dose has shown to be safe, repeated administration may be necessary during prolonged abdominopelvic procedures. Methods This Phase 1 study evaluated the safety, pharmacokinetics and fluorescence properties of repeated nizaracianine dosing in healthy volunteers. Participants received three doses at 0, 1 and 2 h across four dose cohorts: 3 × 0.5, 3 × 1.0, 3 × 2.5 and 3 × 5.0 mg. Safety assessments included vital signs, electrocardiography and laboratory testing. Plasma and urine samples were collected to determine pharmacokinetics. A Foley catheter was used for urine collection and measurement of fluorescence intensity over time. Results Twenty‐one participants were included in the final analysis. Thirty‐six adverse events were reported, mostly related to catheter placement. Nine events were possibly related to nizaracianine. In all cohorts, geometric means of C Max Plasma (61.83, 122.9, 249.2 and 625.7), AUC all (137.0, 276.9, 694.9 and 1835) and half‐life (1.53, 1.52, 1.74 and 1.82) increased, suggesting dose proportionality. Cumulative renal clearance was 65%, indicating possible non‐renal clearance pathways. Fluorescence signals were observed in all cohorts within 5 min of administration, persisting up to 8 h after the first dose. Conclusion Repeated intravenous doses of nizaracianine were well tolerated. PK suggests dose proportionality for C max , AUC (area under the curve of the plasma concentration over time) and half‐life, and fluorescence imaging of urine was possible from 5 min up until 8 h after initial dose.