Room H, 10/16/2000 9: 00 AM - 11: 00 AM (PS) An Alternative Approach Is Necessary to Model the Concentration-Effect Relationship of Mivacurium 

A pharmacokinetic-dynamic explanation of the rapid onset–offset of rapacuronium

“…First, the PK-PD modelling of mivacurium was not improved by incorporation of the model of Donati and Meistelman, although mivacurium is among the most potent neuromuscular blocking agents (expressed as EC 50 in molar units, see Fig. 1) investigated by PK-PD modelling in man [12]. Secondly, we did not find a relation between dose and time to peak effect, as would be predicted by the buffering hypothesis (unpublished data).…”

“…Therefore its small k e0 may be related to the high intrinsic potency according to the buffering hypothesis. However, a PK-PD analysis taking into account the buffering hypothesis could not explain the low value of k e0 [12]. Due to the lack of a sensitive bioanalysis, the PK-PD properties of succinylcholine are still largely unknown.…”

A pharmacokinetic-dynamic explanation of the rapid onset-offset of rapacuronium

“…not taking into account the AChR concentration. 1) investigated by PK-PD modelling in man [12]. This correlation may be explained by the buffering hypothesis.…”

“…In addition, plasma clearance may play a dominant role in the onset time, as was shown by Beaufort and his colleagues [17]. However, a PK-PD analysis taking into account the buffering hypothesis could not explain the low value of k e0 [12]. Nevertheless, the onset time is relatively long due to the small value of k e0 .…”

“…Therefore its small k e0 may be related to the high intrinsic potency according to the buffering hypothesis. However, a PK–PD analysis taking into account the buffering hypothesis could not explain the low value of k e0 [12].…”