Pharmacokinetics and pharmacodynamics of the benzylisoquinolinium muscle relaxants.
The benzylisoquinolinium class of drugs comprises atracurium, 51W89, doxacurium, and mivacurium. Atracurium can be used as a pharmacokinetic benchmark; it has at least two distinct metabolic pathways, of which Hofmann elimination and ester hydrolysis are the most significant. The relative importance of each of these two routes is still a matter of speculation, and this, coupled with the fact that atracurium is a mixture of 10 isomers, has led to the development of many innovative pharmacokinetic modelling concepts. 51W89 is a cis-cis-isomer of atracurium and probably has a pharmacokinetic profile very similar to that of atracurium. Doxacurium, a long-acting benzylisoquinolinium, has a small apparent volume of distribution and an elimination half-time similar to that of pancuronium, and is excreted by the kidneys. Mivacurium is a short-acting benzylisoquinolinium that is rapidly hydrolysed by plasma cholinesterases. Two isomers of mivacurium are very similar, whereas the third isomer differs greatly in both pharmacological activity and elimination half-time, so that analysis requires complex pharmacokinetic methods.
Department of Anaesthesia, University of Newcastle-Upon-Tyne, UK.
C J
CJ
Hull
D001279:Atracurium / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D002802:Cholinesterases / Q000097:blood; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D007536:Isomerism; D007546:Isoquinolines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D000077590:Mivacurium; D008956:Models, Chemical; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; D000077590:Mivacurium; D002802:Cholinesterases; C049429:doxacurium