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

1. Atracurium is a novel bis-quaternary competitive neuromuscular blocking agent designed to undergo rapid non-enzymic inactivation at physiological pH and temperature. 2. Studies of [14C]atracurium in anaesthetized cats using h.p.l.c. techniques showed that the radioactivity eliminated in bile and urine was predominantly metabolites rather than unchanged drug. Both chemical decomposition and enzyme hydrolysis products were observed in vivo. 3. The plasma elimination half life of atracurium after administration via the jugular vein was c. 20 min. Similar results were obtained if the drug was given via the hepatic portal vein or in animals with bilateral renal ligation. These studies indicate that atracurium is rapidly inactivated in vivo and that 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.