ABSTRACT
RATIONALE AND OBJECTIVES: To evaluate the safety and pharmacokinetics of BR21, a liposome-encapsulated iomeprol formulation, in nonpatient volunteers. METHODS: This was a single-blind, placebo-controlled, ascending dose study in 30 adult, male nonpatient volunteers, randomized to receive a single intravenous bolus (2 mL/s) of BR21 (0.5, 1.0, 1.5, 2.0, and 2.5 mL/kg, four volunteers per dose level) or matched volumes of placebo (0.9% saline, 10 volunteers). The safety controls performed consisted of preand postdose complete physical examinations, measurement of vital signs, electrocardiographic controls, clinical laboratory investigations (hematology, serum chemistry, and urinalysis), and monitoring of adverse events. The safety controls and monitoring of subjects for adverse events continued up to 7 days after the dose. For pharmacokinetic analysis, the determination of total iomeprol content was performed by a high-performance liquid chromatography assay procedure in blood, urine, and fecal samples collected before the dose and serially after the dose, up to 120 hours. RESULTS: No serious adverse events occurred throughout the study. All nonserious adverse events were minor and mild in intensity and rapidly resolved without treatment. No difference in the incidence of adverse events was observed among the various doses of BR21 and between BR21 and placebo. There were no clinically significant changes in vital signs, electrocardiographic parameters, or clinical laboratory findings. Iomeprol blood level decay can be described by a three-exponential function, consistent with a distribution phase (range, t1/2 0.12-0.21 hours), a fast elimination phase (range, t1/2 1.2-1.5 hours), and a slow elimination phase from a deep compartment (range, t1/2 3.3-4.5 hours). There was an apparent linearity in the relation between the area under the curve and the dose. Urinary elimination of unchanged iomeprol accounted for 89% to 90% of injected dose within 24 hours. CONCLUSIONS: BR21 appeared to be safe and well tolerated in nonpatient subjects. Its pharmacokinetic profile was compatible with nonspecific distribution into the extracellular fluid space and specific distribution into a deep compartment.
