Inhibition of hepatic microsomal drug metabolism by atracurium administration in the rat.
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.
Böhrer
H
H
Department of Anaesthesia, University of Heidelberg, Germany.
Schmidt
H
H
Bach
A
A
Martin
E
E
Kohl
B
B
Bolsen
K
K
Goerz
G
G
D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001279:Atracurium / Q000008:administration & dosage / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006439:Hemodynamics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009929:Organ Size; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010197:Pancuronium / Q000008:administration & dosage / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014673:Vecuronium Bromide / Q000008:administration & dosage / Q000494:pharmacology
D065607:Cytochrome P-450 Enzyme Inhibitors; D001279:Atracurium; D014673:Vecuronium Bromide; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase; D010197:Pancuronium