Effects of hepatic uptake of vecuronium bromide and its putative metabolites on their neuromuscular blocking actions in the cat

Abstract

The neuromuscular blocking effects of equipotent doses of the three putative metabolites of vecuronium (3-hydroxy vecuronium, 17-hydroxy vecuronium and 3,17-dihydroxy vecuronium) were compared with those of an equipotent dose of vecuronium. Results obtained with the liver excluded from the circulation and after intraportal injection were compared with those following i.v. injection, in the cat. Following injection i.v., and with the liver excluded from the systemic circulation, there was a marked prolongation of duration of action (which averaged 100%) with all four compounds. After intraportal injection the only significant results were shortening of the duration of action and a decrease in the maximum blockade achieved with the 3-hydroxy metabolite. It is concluded that, in the cat, the hepatic removal of these compounds from the circulation is a major determinant of their duration of action. This process seems to be of importance for all four compounds, although the 3-hydroxy derivative appeared the most sensitive.