Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent

Rationale and objectives: Gadomer-17 is, a new magnetic resonance (MR) cont rast medium presently in clinical development, It is a dendritic gadolinium (Gd) chelate carrying 24. Gd ions. This study investigated the pharmacokin etic behavior of this contrast medium. Methods: The pharmacokinetics of Gad omer-17 were investigated in different species (rat, rabbit, dog, monkey). for up to 7 days after intravenous (i.v.) injection of 25-100 mu mol/kg bod y weight. In addition, elimination and biodistribution were evaluated after single Lv. injection of Gadomer-17 in rats. Results: After i.v. injection Gadomer-17 distributes almost exclusively within the intravascular space wi thout significant diffusion into the interstitial space. The volume of dist ribution (Ve) in the initial or alpha -phase ranged from 0.04 1/kg (rats, r abbits.) 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 s pace. After single i.v. injection in rats, the dendritic contrast medium wa s rapidly and completely eliminated from the body, mainly via glomerular fi ltration. No long-term accumulation or retention of the nonmetabolized agen t was detectable in organs or tissues. Conclusions: Gadomer-17 is a promisi ng new MR contrast medium that has an intravascular distribution and a rapi d renal elimination. (C) 2001 Elsevier Science B.V. All rights reserved.