Estimation of the plasma-effect-site equilibration rate constant (k e0) of rocuronium by the time of maximum effect: A comparison with non-parametric and parametric approaches

Abstract

Background. The first order plasma-effect-site equilibration rate constant (ke0) links the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. For the calculation of the ke0, one method uses a single point of the response curve corresponding to the time to peak effect of a drug (tpeak); however, it has not been validated. This study compares the ke0 calculated with the method of tpeak and the k e0 calculated with traditional non-parametric and parametric methods. Methods. Fifteen adult patients receiving total intravenous anaesthesia (TIVA) were studied. All patients were monitored with an NMT Monitor 221 (GE Healthcare, Helsinki, Finland) to obtain the evoked compound EMG of the adductor pollicis to a train-of-four stimuli at 10 s intervals. During TIVA, rocuronium 0.15 mg kg-1 was given i.v. as a bolus, and the neuromuscular response was recorded until recovery from block. Using the tpeak and the complete response curve, ke0 of rocuronium was calculated with the three methods using the predicted plasma concentrations of rocuronium from a PK model. Values of ke0 are median (range). Results. The k e0s obtained were 0.19 min-1 (0.09-0.72) with the 't peak' method, 0.20 min-1 (0.14-0.44) with the non-parametric method, and 0.19 min-1 (0.11-0.38) [typical value (range)] with the parametric method (NS). Conclusions. If the tpeak can be adequately estimated from the data, the 'tpeak method' is a valid alternative to traditional methods to calculate the ke0. © The Board of Management and Trustees of the British Journal of Anaesthesia 2007. All rights reserved.