Preclinical safety evaluation of Gd-EOB-DTPA (Primovist).
OBJECTIVE
Gadoxetic acid [gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA); Primovist] is a liver specific contrast agent for magnetic resonance imaging. For risk assessment of the single diagnostic use the toxicity of this compound was assessed.


METHODS
Studies into acute, repeated-dose, reproductive and developmental toxicity, and local tolerance, contact sensitizing, and genotoxic potential were performed.


RESULTS
Lethality was observed after a single intravenous administration at doses 2 orders of magnitude higher than the clinical dose. The no observed adverse effect levels after repeated administration markedly exceeds the single diagnostic dose in humans and no unexpected organ toxicity was observed. No indications of reproductive and developmental toxicity, potential contact allergenic, and genotoxic effects were observed. Gd-EOB-DTPA was well tolerated after intravenous administration.


CONCLUSIONS
Gd-EOB-DTPA was well tolerated with high safety margins between the single diagnostic dose and the doses showing adverse effects in animal studies.
Döhr
Olaf
O
Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.
Hofmeister
Rainer
R
Treher
Marianne
M
Schweinfurth
Hermann
H
D000818:Animals; D003287:Contrast Media / Q000494:pharmacology / Q000633:toxicity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D019786:Gadolinium DTPA / Q000494:pharmacology / Q000633:toxicity; D006168:Guinea Pigs; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D019055:No-Observed-Adverse-Effect Level; D011817:Rabbits; D051381:Rats; D018675:Toxicity Tests
D003287:Contrast Media; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA