Métabolisme et pharmacocinétique de l'atracurium

Abstract

Atracurium is a new neuromuscular blocking agent which has an unique mode of elimination by spontaneous degradation in slightly alkali solution, according to the Hofmann elimination. The Hofmann elimination is completed in plasma ( in vitro or in vivo) by an ester hydrolysis. The major degradation product is laudanosine. Metabolites can be considered as pharmacologically inactive with the usual doses of atracurium. Spontaneous degradation of atracurium in plasma is the major route of elimination in man and contributes to a short elimination half-life (approximatively 20 min). Distribution half-life is short and central and peripheral volumes are small when compared with the usual neuromuscular blocking agents. The pharmacokinetic parameters give a rapid dynamic equilibrium so that incremental doses will not lead to accumulation phenomenon. Because of spontaneous degradation of atracurium in plasma, its kinetics are theoretically independent of renal and liver functions. Only a slight increase of distribution volumes can be seen in very severe renal/hepatic failure. Atracurium pharmacokinetics could theoretically be modified by some modifications of acid-base equilibrium or alterations of thermoregulation. Pharmacokinetic studies are not yet available in these areas.