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Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent
Authors:Bernd Misselwitz  Heribert Schmitt-Willich  Wolfgang Ebert  Thomas Frenzel  Hanns-Joachim Weinmann
Affiliation:(1) Research Laboratories of Schering AG, D-13342 Berlin, Germany;(2) Present address: Schering AG, Diagnostic Imaging Division. Contrast Media Research, Müllerstr. 178, D-13342 Berlin, Germany
Abstract:Rationale and objectives: Gadomer-17 is a new magnetic resonance (MR) contrast medium presently in clinical development. It is a dendritic gadolinium (Gd) chelate carrying 24 Gd ions. This study investigated the pharmacokinetic behavior of this contrast medium. Methods: The pharmacokinetics of Gadomer-17 were investigated in different species (rat, rabbit, dog, monkey) for up to 7 days after intravenous (i.v.) injection of 25–100 μmol/kg body weight. In addition, elimination and biodistribution were evaluated after single i.v. injection of Gadomer-17 in rats. Results: After i.v. injection Gadomer-17 distributes almost exclusively within the intravascular space without significant diffusion into the interstitial space. The volume of distribution (Vc) in the initial or α-phase ranged from 0.04 1/kg (rats, rabbits) to 0.06 1 kg (monkeys) and 0.07 1/kg (dogs), which reflects mainly the plasma volume. The blood/plasma concentration profile was found to be biphasic. The volume of distribution at a steady state is clearly smaller than that of other contrast media, which distribute to the extracellular space. After single i.v. injection in rats, the dendritic contrast medium was rapidly and completely eliminated from the body, mainly via glomerular filtration. No long-term accumulation or retention of the nonmetabolized agent was detectable in organs or tissues. Conclusions: Gadomer-17 is a promising new MR contrast medium that has an intravascular distribution and a rapid renal elimination.
Keywords:MR imaging  Contrast agents  Gadomer-17  Pharmacokinetics  Experimental studies  Blood pool agents
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