Safety, Tolerance, and Pharmacokinetics of High Doses of Gadodiamide Injection, a Nonionic Magnetic Resonance Imaging Contrast Agent

Abstract

Rationale and Objectives. Doses of up to 0.3 mmol/kg of gadodiamide injection have been used clinically to provide contrast enhancement in MR imaging of the central nervous system. This double-blind study evaluated the safety, tolerance, and pliarmacokinetics of gadodiamide doses of 0.5–1.5 mmol/kg administered intravenously. Methods. Groups of seven healthy adults were assigned randomly to receive either a placebo (two subjects per group) or one of five ascending doses (0.5, 0.75, 1.0, 1.25, or 1.5 mmol/kg) of gadodiamide (five subjects per group). Results. The frequencies of adverse events and injection-associated discomfort, all of which were nonserious, were statistically similar for gadodiamide and placebo subjects. Flushing occurred more frequently in those subjects having received gadodiamide. No clinically significant effects on vital signs or laboratory values were observed. Gadodiamide was rapidly eliminated from the serum (half-life of approximately 2 hr) and exhibited linear pharmacokinedcs. Nearly the entire dose was recovered in the urine as unmetabolized gadodiamide. Conclusion. Gadodiamide doses of 0.5–1.5 mmol/kg were safe and well tolerated in healthy adults, with no dose-related trends observed in adverse events or other safety parameters. The pharmacokinetics were consistent with those observed for lower doses. Rationale and Objectives. Doses of up to 0.3 mmol/kg of gadodiamide injection have been used clinically to provide contrast enhancement in MR imaging of the central nervous system. This double-blind study evaluated the safety, tolerance, and pliarmacokinetics of gadodiamide doses of 0.5–1.5 mmol/kg administered intravenously. Methods. Groups of seven healthy adults were assigned randomly to receive either a placebo (two subjects per group) or one of five ascending doses (0.5, 0.75, 1.0, 1.25, or 1.5 mmol/kg) of gadodiamide (five subjects per group). Results. The frequencies of adverse events and injection-associated discomfort, all of which were nonserious, were statistically similar for gadodiamide and placebo subjects. Flushing occurred more frequently in those subjects having received gadodiamide. No clinically significant effects on vital signs or laboratory values were observed. Gadodiamide was rapidly eliminated from the serum (half-life of approximately 2 hr) and exhibited linear pharmacokinedcs. Nearly the entire dose was recovered in the urine as unmetabolized gadodiamide. Conclusion. Gadodiamide doses of 0.5–1.5 mmol/kg were safe and well tolerated in healthy adults, with no dose-related trends observed in adverse events or other safety parameters. The pharmacokinetics were consistent with those observed for lower doses.