Inhibition of Hepatic Microsomal Drug Metabolism by Atracurium Administration in the Rat

Abstract

The muscle relaxant atracurium is known to undergo extrahepatic degradation via Hofmann elimination and ester hydrolysis. The purpose of the present study was to evaluate the effects of atracurium on hepatic P450-dependent enzyme activities. Thirty-two male Sprague-Dawley rats were anaesthetized, mechanically ventilated, and randomly allocated to one of four study groups: group 1 received saline, group 2 atracurium, group 3 vecuronium, and group 4 pancuronium intravenously for a period of 3 hr. Equipotent doses of the muscle relaxants were applied; the doses had been obtained in a pilot study using evoked electromyography. At the end of the study period, the livers were removed and analyzed. All three muscle relaxants may lead to inhibition of hepatic drug metabolism. Atracurium influences hepatic P450, although it is predominantly degraded in extrahepatic tissues. Further studies are needed to evaluate the contribution of the major metabolite laudanosine to this inhibitory action.

Effects of Premedication Medicines on the Formation of the CYP3A4‐Dependent Metabolite of Ropivacaine, 2′, 6′‐Pipecoloxylidide, on Human Liver Microsomes in vitro

“…Ono et al (1996) used a recombinant vaccinia virus system and showed that the metabolism of diazepam in HepG2 cells is mediated by CYP3A4 as well as CYP2C19, which has been reported as a polymorphic enzyme, in human liver. Vecuronium is subject to the catalytic activity of CYP1A1 and CYP2B in rat microsomes (Bohrer et al 1993) while cimetidine and clonidine are not known to undergo CYP‐catalyzed metabolism.…”

A study of the in vitro interaction between lidocaine and premedications using human liver microsomes*

“…Ono et al (16) using a recombinant vaccinia virus system, showed that the metabolism of diazepam in HepG2 cells is mediated by CYP3A4 as well as CYP2C19, which has been reported as a polymorphic enzyme, in human liver. Vecuronium and pancuronium are subject to the catalytic activity of CYP1A1 and CYP2B in rat microsomes (17). However, pentobarbital, cimetidine, suxamethonium and clonidine are not known to undergo P450-catalysed metabolism.…”

A study of the in vitro clinical interaction between lidocaine and premedications using rat liver microsomes

“…Vecuronium and pancuronium are subject to the catalytic activity of CYP1A1 and CYP2B in rat microsomes. 8 On the other hand, pentobarbital, cimetidine, suxamethonium and clonidine are not known to undergo P450-catalyzed metabolism.…”