title: Volume of the effect compartment in simulations of neuromuscular block.
abstract: BACKGROUND
  The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants.
  
  
  METHODS
  The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent receptor concentration in the effect compartment is the ratio of this amount and the volume arbitrarily assigned to the effect compartment. The muscle relaxants were postulated to diffuse between the central and the effect compartment and to bind to the postsynaptic receptors. NMB was calculated from the free concentration of the muscle relaxant in the effect compartment.
  
  
  RESULTS
  The simulations suggest that the time profiles of NMB and the derived pharmacokinetic and pharmacodynamic variables are dependent on the apparent receptor concentration in the effect compartment. For small, but not for large, volumes, times to peak submaximal NMB are projected to depend on the magnitude of NMB and on the binding affinities.
  
  
  CONCLUSIONS
  An experimental design to estimate the volume of the effect compartment is suggested.
authors.affiliation: Department of Anesthesiology, Medical University of Ohio, Toledo, OH, USA. vnigrovic@meduohio.edu
authors.forename: Vladimir
authors.initials: V
authors.lastname: Nigrovic
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Proost
authors.forename: Anton
authors.initials: A
authors.lastname: Amann
authors.forename: Shashi B
authors.initials: SB
authors.lastname: Bhatt
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008954:Models, Biological; D008962:Models, Theoretical; D009045:Motor Endplate / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000493:pharmacokinetics / Q000494:pharmacology; D019148:Neuromuscular Blockade; D009468:Neuromuscular Diseases / Q000188:drug therapy / Q000378:metabolism; D013997:Time Factors
chemical_list: D009125:Muscle Relaxants, Central