Pharmacokinetics of atracurium.

Sir,—We congratulate Drs Beetner, Bjorksten and Crankshaw on their description of the pharmacokinetics of atracurium [1]. As they observe correctly, the derivation of pharmacokinetic parameters after a single bolus dose is subject to difficulties because of the presumed degradation of atracurium in sites peripheral to the plasma. In our view, however, the crucial flaw in previous attempts to describe the pharmacokinetics of atracurium (including our own, [2]), is not that the observations were not made at steady state, but that it is impossible to define the rate of peripheral degradation of atracurium on the basis of measurements made on plasma samples alone [3]. The application of standard formulae allows an objective summary of data, and comparison between groups, and may thus be useful. It does not allow calculation of the plasma clearance or steady state volume of distribution as usually denned [4]. We wish to point out that the method of analysis used by Beemer and colleagues does not overcome the problems created by the peripheral degradation of atracurium. The application of his equation (3) gives an estimate of clearance which is not equivalent to plasma clearance, denned as the volume of plasma theoretically completely cleared of drug per unit time. Indeed it may be re-written: