PHARMACOKINETICS AND PHARMACODYNAMICS OF THE BENZYLISOQUINOLINIUM MUSCLE-RELAXANTS

The benzylisoquinolinium class of drugs comprises atracurium, 51W89, d oxacurium, and mivacurium. Atacurium can be used as a pharmacokinetic benchmark; it has at least two distinct metabolic pathways, of which H ofmann elimination and ester hydrolysis are the most significant. The relative importance of each of these two routes is still a matter of s peculation, and this, coupled with the fact that atracurium is a mixtu re of 10 isomers, has led to the development of many innovative pharma cokinetic modelling concepts. 51W89 is a cis-cis-isomer of atracurium and probably has a pharmacokinetic profile very similar to that of atr acurium. Doxacurium, a long-acting benzylisoquinolinium, has a small a pparent 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-lime, so that analysis requires complex pharmacokinet ic methods.