The pharmacokinetic profile, tolerability and safety of the iodinated, non-ionic, dimeric contrast medium Iosimenol 340 injection in healthy human subjects

Abstract

Background: Iosimenol 340 injection is a new isotonic iodinated contrast medium for X-ray angiography.

Purpose: To investigate the pharmacokinetics and biotransformation, tolerability, and safety of Iosimenol 340 in healthy human subjects.

Material and methods: Twenty-four subjects were enrolled and randomized to receive either Iosimenol 340 (0.5, 1.5 or 3.0 mL/kg) or placebo (0.9% saline). In each dosing group, six subjects received Iosimenol 340 and two subjects received placebo. Safety was assessed by physical examination, vital signs, electrocardiography, and laboratory tests. Adverse events were recorded throughout the study up to 14 days after dosing. Blood samples were collected from 10 min before until 48 h after the start of dosing and urine samples were collected from 15 min before until 96 h after the start of dosing. Iosimenol was quantified in plasma and urine by measuring iodine concentrations with X-ray fluorescence. High-performance liquid chromatography was used to assess iosimenol biotransformation.

Results: Mean half-lives (mean ± standard deviation [SD]) of iosimenol were 0.17 ± 0.08 h (10.2 ± 4.8 min) and 2.01 ± 0.32 h for distribution and terminal elimination phases, respectively. The apparent volume of distribution was 0.27 ± 0.05 L/kg, indicating distribution to the extracellular fluid volume. Iosimenol was excreted within 24 h without any sign of metabolic transformation. Thirty-two adverse events were observed in 14 subjects. All were mild or moderate, and were transient in nature.

Conclusion: Iosimenol was not metabolized, had a distribution volume corresponding to the extracellular space, and was rapidly excreted through the kidneys by glomerular filtration. The area under the plasma concentration curve and the peak plasma concentration was proportional to dose, while clearance was independent of dose. Iosimenol 340 was well tolerated.

Keywords: Iosimenol; iodinated contrast media; pharmacokinetics; phase I; safety.