Author:
Hofmann Birte Maria,Riecke Kai,Klein Stefan,Berse Matthias,Rottmann Antje,Sutter Gabriele,Ebert Wolfgang
Abstract
Objectives
Gadolinium (Gd)–based contrast agents are well established in clinical routine and have been proven safe and effective. However, there is a need for “next-generation” Gd-based contrast agents that would allow lowering the Gd dose used for routine contrast-enhanced magnetic resonance imaging procedures. The objective of this first-in-human study was to investigate the pharmacokinetic profile, safety, and tolerability of gadoquatrane, a novel high-relaxivity Gd-based contrast agent.
Materials and Methods
This study was conducted in 2018/2019 as a prospective, randomized, single-blind, single-dose, placebo-controlled, escalating-dose study. Healthy volunteers were randomly assigned (6:2) to intravenous administration of gadoquatrane (0.025 to 0.2 mmol Gd/kg body weight) or placebo. Study procedures included collection of blood samples and excreta for pharmacokinetic analyses and safety assessments.
Results
Forty-nine healthy study participants (mean age ± SD, 35 ± 6.3 years; 24 female) were evaluated. The effective half-life of gadoquatrane in plasma was short and similar in all dose groups (1.4–1.7 hours). Plasma concentrations around the lower quantitation limit (0.0318 μmol Gd/L) were reached 15–72 hours after administration. The volume of distribution at steady state was ~0.2 L/kg in all dose groups. The clearance (total and renal) was ~0.1 L/h per kilogram in all groups. Across dose groups, the exposure of gadoquatrane increased dose-proportionally. Metabolite profiling revealed no hint of degradation in vivo or release of free Gd. Seven of 36 participants (19.4%) receiving gadoquatrane and 4 of 13 participants (30.8%) receiving placebo experienced mild or moderate treatment-emergent adverse events. No serious adverse events occurred. The analysis of the Gd concentration-QTc interval relationship indicated no risk of QT/QTc prolongation (>10 milliseconds) with gadoquatrane at clinical dose levels.
Conclusions
Gadoquatrane with its high-relaxivity, pharmacokinetic similarity to established Gd-based contrast agents and high tolerability is a promising “next-generation” contrast agent for magnetic resonance imaging.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Radiology, Nuclear Medicine and imaging,General Medicine
Cited by
2 articles.
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