Metabolic studies in the cat with atracurium: a neuromuscular blocking agent designed for non-enzymic inactivation at physiological pH

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Abstract
Atracurium is a novel bis-quaternary competive neuromuscular blocking agent designed to undergo rapid non-enzymic inactivation at physiological pH and temperature. Studies of [14C]atracurium in anesthetized cats using h.p.l.c. [high performance liquid chromatography] techniques showed that the radioactivity eliminated in bile and ureine was predominantly metabolites rather than unchanged drug. Both chemical decomposition and enzyme hydrolysis products were observed in vivo. The plasma elimination half life of atracurium after administration via the jugular vein was .apprx. 20 min. Similar results were obtained if the drug was given via the hepatic portal vein or in animals with bilateral renal ligation. Evidently atracurium is rapidly inactivated in vivo and neither the liver nor the kidneys play a major role in its metabolism or elimination, in accord with the premise on which the drug molecule was designed.

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