PHYSICOCHEMICAL PROPERTIES, PHARMACOKINETICS, AND BIODISTRIBUTION OF GADOTERIDOL INJECTION IN RATS AND DOGS

Rationale and Objectives. The physicochemical properties of gadoterido l, a macrocyclic nonionic gadolinium complex, were studied together wi th its pharmacokinetics and biodistribution in rats and dogs. Methods. Studies in rats Mere conducted after single intravenous injections at 0.1 or 0.35 mmol/kg using Gd-153-labeled gadoteridol or with seven da ily doses of 0.1 mmol/kg to examine the levels of residual gadolinium in organs. Nonradioactive biodistribution and excretion studies were p erformed in dogs following injection at 0.1 mmol/kg. Results. After in jection, the dose was rapidly cleared from rat blood and excreted such that more than 90% of the dose appeared in the urine within 4 hr of i njection. At 7 and 14 days postinjection, only extremely low levels of gadolinium were observed in liver and bone; these levels were two to eight times lower than the levels reported after the injection of gado pentetate dimeglumine. Conclusion. The extracellular distribution and rapid urinary excretion of gadoteridol is in agreement with data obtai ned with other gadolinium-containing chelates used as intravascular ma gnetic resonance imaging contrast agents. Differences observed in the long-term retention of gadolinium between gadoteridol and gadopentetat e dimeglumine were consistent with the reported greater in vivo resist ance to transmetallation of gadolinium macrocycles compared with the l inear gadolinium chelate molecules.