A Pharmacokinetics, Efficacy, and Safety Study of Gadoterate Meglumine in Pediatric Subjects Aged Younger Than 2 Years

Invest Radiol. 2018 Feb;53(2):70-79. doi: 10.1097/RLI.0000000000000412.


Objectives: The primary objective of this study was to investigate the pharmacokinetic profile of gadoterate meglumine in pediatric patients younger than 2 years; the secondary objectives were to document its efficacy and safety.

Material and methods: This was a Phase IV open-label, prospective study conducted in 9 centers (4 countries). Forty-five patients younger than 2 years with normal estimated glomerular filtration rate and scheduled to undergo routine gadolinium-enhanced magnetic resonance imaging (MRI) of any organ were included and received a single intravenous injection of gadoterate meglumine (0.1 mmol/kg). To perform the population pharmacokinetics analysis, 3 blood samples per subject were drawn during 3 time windows at time points allocated by randomization.

Results: Gadoterate meglumine concentrations were best fitted using a 2-compartmental model with linear elimination from central compartment. The median total clearance adjusted to body weight was estimated at 0.06 L/h per kg and increased with estimated glomerular filtration rate according to a power model. The median volume of distribution at steady state (Vss) adjusted to body weight was estimated at 0.047 L/kg. Estimated median terminal half-life (t1/2β) was 1.35 h, and the median systemic exposure (area under the curve) was 1591 μmol h/L. Efficacy was assessed by comparing precontrast +postcontrast images to precontrast images in a subset of 28 subjects who underwent an MRI examination of brain, spine, and associated tissues. A total of 28 lesions were identified and analyzed in 15 subjects with precontrast images versus 30 lesions in 16 subjects with precontrast + postcontrast images. Lesion visualization was improved with a mean (SD) increase in scores at subject level of 0.7 (1.0) for lesion border delineation, 0.9 (1.6) for internal morphology, and 3.1 (3.2) for contrast enhancement. Twenty-six adverse events occurred postinjection in 13 subjects (28.9%), including 3 serious reported in 1 subject (2.2%). One subject (2.2%) experienced 1 rash of moderate intensity considered as related to gadoterate meglumine.

Conclusions: The pharmacokinetic profile of gadoterate meglumine after a single intravenous injection of 0.1 mmol/kg was appropriately described in newborns and infants younger than 2 years, for whom no dose adjustment is required. The improved efficacy of gadoterate meglumine for contrast-enhanced MRI examination of brain, spine, and associated tissues, as well as its good safety profile, was also demonstrated in this population.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / diagnostic imaging
  • Contrast Media / adverse effects
  • Contrast Media / pharmacokinetics*
  • Female
  • Gadolinium
  • Glomerular Filtration Rate
  • Humans
  • Image Enhancement / methods*
  • Infant
  • Infant, Newborn
  • Injections, Intravenous
  • Magnetic Resonance Imaging / methods
  • Male
  • Meglumine / adverse effects
  • Meglumine / pharmacokinetics*
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / pharmacokinetics*
  • Prospective Studies
  • Spine / diagnostic imaging


  • Contrast Media
  • Organometallic Compounds
  • Meglumine
  • Gadolinium
  • gadoterate meglumine