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

Abstract

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.

• Authors: T Staks, G Schuhmann-Giampieri, T Frenzel, H J Weinmann, L Lange, J Platzek
• Journal: Investigative radiology (Invest Radiol) Vol. 29 Issue 7 Pg. 709-15 (Jul 1994) ISSN: 0020-9996 [Print] United States
• PMID: 7960618 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

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