title: 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.
  
  
  OBJECTIVE
  To investigate the pharmacokinetics and biotransformation, tolerability, and safety of Iosimenol 340 in healthy human subjects.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Otsuka Novel Products GmbH, Munich, Germany, Germany kmeurer@otsuka-onpg.com.
authors.forename: Karoline
authors.initials: K
authors.lastname: Meurer
authors.affiliation: Department of Radiology, Charité, Humboldt University, Berlin, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Kelsch
authors.affiliation: Otsuka Novel Products, Medical Imaging, Otsuka Pharmaceutical Development & Commercialization, Princeton, NJ, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Hogstrom
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001549:Benzamides / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003287:Contrast Media / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects / Q000379:methods; D005076:Exanthema / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010808:Physical Examination / Q000379:methods; D011412:Propanolamines / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D011537:Pruritus / Q000139:chemically induced; D012016:Reference Values; D012965:Sodium Chloride / Q000008:administration & dosage; D055986:Vital Signs / Q000187:drug effects; D055815:Young Adult
chemical_list: D001549:Benzamides; D003287:Contrast Media; D011412:Propanolamines; D012965:Sodium Chloride; C450045:iosmin
keywords: Iosimenol; iodinated contrast media; pharmacokinetics; phase I; safety