Estimation of the plasma effect-site equilibration rate constant (ke0) of rocuronium by the time of maximum effect: a comparison with non-parametric and parametric approaches.
BACKGROUND
The first order plasma-effect-site equilibration rate constant (k(e0)) links the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. For the calculation of the k(e0), one method uses a single point of the response curve corresponding to the time to peak effect of a drug (t(peak)); however, it has not been validated. This study compares the k(e0) calculated with the method of t(peak) 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 t(peak) and the complete response curve, k(e0) of rocuronium was calculated with the three methods using the predicted plasma concentrations of rocuronium from a PK model. Values of k(e0) are median (range).


RESULTS
The k(e0)s 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 t(peak) can be adequately estimated from the data, the 't(peak) method' is a valid alternative to traditional methods to calculate the k(e0).
Departamento de Anestesiología, Facultad de Medicina, Hospital Clínico U.C., Pontificia Universidad Católica de Chile, PO Box 114-D, Marcoleta 367, Santiago, Chile. licorti@med.puc.cl
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D000293:Adolescent; D000328:Adult; D000732:Androstanols / Q000097:blood* / Q000494:pharmacology; D000771:Anesthesia, Intravenous; D004558:Electric Stimulation; D004576:Electromyography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods; D019148:Neuromuscular Blockade; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood* / Q000494:pharmacology; D000077123:Rocuronium; D012815:Signal Processing, Computer-Assisted; D018709:Statistics, Nonparametric
D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium