Pharmacokinetics, dose proportionality, and tolerability of gadobutrol after single intravenous injection in healthy volunteers

Invest Radiol. 1994 Jul;29(7):709-15. doi: 10.1097/00004424-199407000-00008.


Rationale and objectives: Gadobutrol is a new gadolinium-based hydrophilic and neutral macrocyclic contrast medium for magnetic resonance imaging. In this article, the authors report on the first application of gadobutrol in humans, up to a dose of 0.5 mmol/kg.

Methods: Gadobutrol was investigated after single intravenous administration in two phase-1 studies testing low (0.5 mol/L) and high concentrations (1 mol/L) in healthy, male volunteers using a double-blind, randomized, placebo-controlled study with n = 55 for the low concentration (0.04, 0.1, 0.2, 0.3, and 0.4 mmol/kg body weight), followed by n = 36 for the high concentration (0.3, 0.4, and 0.5 mmol/kg body weight). Vital signs and laboratory parameters were measured for all dose groups investigated, whereas for the calculation of the pharmacokinetic parameters, the dose groups 0.04, 0.1, and 0.4 mmol/kg body weight were selected.

Results: Gadobutrol was well tolerated up to doses of 0.5 mmol/kg, and no relevant changes in vital signs and laboratory parameters occurred. The terminal disposition half-life of gadobutrol in plasma was approximately 1.5 hours. Total clearance approximated renal clearance and approximated the value of 120 mL/min, indicating glomerular filtration as the main pathway of elimination. The steady-state volume of distribution indicated predominantly extracellular distribution of gadobutrol. No metabolites were detected. The renal excretion rate was linear over the large dose range tested, indicating dose-proportionate, first-order kinetics of gadobutrol.

Conclusion: Single intravenous administration of gadobutrol was well tolerated up to the dose level of 0.5 mmol/kg body weight. These factors suggest that gadobutrol will be a safe magnetic resonance imaging contrast agent.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Contrast Media / administration & dosage
  • Contrast Media / metabolism
  • Contrast Media / pharmacokinetics*
  • Contrast Media / pharmacology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Tolerance
  • Feces / chemistry
  • Gadolinium / administration & dosage
  • Gadolinium / metabolism
  • Gadolinium / pharmacokinetics*
  • Gadolinium / pharmacology
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Male
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacokinetics*
  • Organometallic Compounds / pharmacology
  • Placebos
  • Safety


  • Contrast Media
  • Organometallic Compounds
  • Placebos
  • gadobutrol
  • Gadolinium