Document Detail

Onset-potency relationship of nondepolarizing muscle relaxants: a reexamination using simulations.
MedLine Citation:
PMID:  17901887     Owner:  NLM     Status:  MEDLINE    
Nondepolarizing muscle relaxants (MRs) display an inverse onset-potency relationship, that is, less potent MRs display a more rapid onset. We have conducted the current investigation to estimate the impact of variable pharmacokinetic or pharmacodynamic properties of the MRs on potency and onset time, and on the onset-potency relationship. Using a model of neuromuscular transmission, we changed either the affinity of MRs for the postsynaptic receptors or the pharmacokinetic properties of the MRs. The elimination rate constant, k(10), which defines the systemic clearance, was assigned one of 9 values and the transport rate constant, k(12), one of 5 values. The transport rate constant into the effect compartment was constant (k(e1) = 0.2 min(-1)). Only one parameter was altered at a time. With constant pharmacokinetics, a 100-fold decrease in affinity caused a proportional decrease in potency, but little change (0.02 min) in onset time. With constant affinity, increasing the clearance from 1 to 250 mL x kg(-1) x min(-1) shortened the onset time from 7.2 to 0.7 min and decreased the potency 12-fold. In a double logarithmic plot, the onset-potency relationship was linear. Lesser affinities produce a nearly parallel rightward shift of the regression lines. The inverse onset-potency relationship may be explained by the pharmacokinetic factors producing changes in both the potency and onset times.
S B Bhatt; A Amann; V Nigrovic
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  85     ISSN:  0008-4212     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-09-28     Completed Date:  2007-11-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  774-82     Citation Subset:  IM    
Department of Anesthesiology, College of Medicine, University of Toledo, 3000 Arlington Avenue, Toledo, OH 43614-2598, USA.
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MeSH Terms
Computer Simulation*
Metabolic Clearance Rate
Neuromuscular Blockade
Neuromuscular Nondepolarizing Agents / pharmacokinetics,  pharmacology*
Reg. No./Substance:
0/Neuromuscular Nondepolarizing Agents

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