Gadodiamide injection. First human experience with the nonionic magnetic resonance imaging enhancement agent

The safety, tolerance, and pharmacokinetics of gadodiamide injection (Omniscan, Sanofi Winthrop Pharmaceuticals, New York, NY) were evaluated in an open, ascending-dose study in 20 healthy male volunteers. Gadodiamide injection was administered intravenously at doses of 0.05, 0.1, 0.2, and 0.3 mmol/kg. Mild adverse events were experienced by nine subjects. These events included, but were not limited to, light-headedness, dizziness, and perversion of taste or smell. There was one occurrence of injection-associated discomfort that resolved within seconds. Vital sign and electrocardiogram measurements did not show any clinically relevant changes. There were no clinically significant changes in laboratory parameters, but minor transient elevations in serum iron were detected. These elevations typically occurred 8 and 48 hours after administration of gadodiamide injection and were not dose related. The pharmacokinetics of gadodiamide injection were evaluated in the 0.1-mmol/kg and 0.3-mmol/kg dose groups with the serum time-concentration data fitted to an open two-compartment model and the urine time-concentration data fitted to a one-compartment model. The serum elimination half-life was approximately 70 minutes, and urinary recovery was greater than 95% by 72 hours after administration.