Pharmacokinetics, pharmacodynamics and dose-response relationships of atracurium administered i.v.

A complete pharmacokinetic and pharmacodynamic model for the novel non-depolarizing neuromuscular blocking agent atracurium is proposed, which accounts for tetanic and single twitch responses after any i.v. administration of this drug. The means and standard deviations of the kinetic parameters are given from studies in 19 patients, and the pharmacodynamic parameters from eight patients in whom plasma drug concentrations and dynamic responses were recorded concurrently. Similarities in dynamic parameters are noted for atracurium administered to cats, and for other non-depolarizing neuromuscular blocking agents in man. The use of this approach allows clinicians to understand and rationalize all the features associated with the time-course of blockade after varied i.v. regimens, but more importantly, allows them to design any required neuromuscular blocking profile which will also result in minimal drug loading of their patients.