Summary of preclinical safety evaluation of gadoteridol injection.

RATIONALE AND OBJECTIVES

To support clinical use of gadoteridol (0.5 M) injection, a battery of in vitro and in vivo safety studies was conducted.

RESULTS

In mice, the acute intravenous LD50 for gadoteridol (0.5 M) injection was 11 to 14 mmol/kg, and the intravenous minimal lethal dose in rats was greater than 10 mmol/kg. In 2-week studies with gadoteridol, no serious effects were observed in mice given 3 mmol/kg or dogs given 1.5 mmol/kg daily. In a series of reproduction studies, no treatment-related adverse effects on fertility, reproductive performance, or postnatal development were seen in rats at doses of 1.5 mmol/kg or less, and no teratogenic effects were observed at doses as high as 6 mmol/kg in rabbits and 10 mmol/kg in rats. In an in vitro test, gadoteridol did not demonstrate any potential to hemolyze human erythrocytes when incubated in high concentrations with whole blood, suggesting there is little probability gadoteridol will cause hemolysis in vivo.

CONCLUSIONS

A substantial margin of safety exists for the clinical use of gadoteridol in magnetic resonance imaging procedures.