Anästhesiol Intensivmed Notfallmed Schmerzther 2000; 35(2): 9-8
DOI: 10.1055/s-2000-10850-2
MINI-SYMPOSIUM
Georg Thieme Verlag Stuttgart ·New York

Pharmacokinetic Aspects of the Onset of Action of Neuromuscular Blocking Agents

J. H.  Proost, J.  M. K. H. Wierda
  • Research Group for Experimental Anaesthesiology and Clinical Pharmacology, Department of Anaesthesiology, University Hospital, Groningen, The Netherlands
Further Information

Publication History

Publication Date:
12 May 2004 (online)

Introduction

In order to understand the factors governing the onset of neuromuscular block, it is important to know the processes following administration of a neuromuscular blocking agent (NMBA), eventually resulting in neuromuscular block. With respect to the processes involved in the time course of neuromuscular block, four steps can be discerned:

Distribution and elimination of the NMBA, i. e., pharmacokinetics; Transport of the NMBA from the blood to the receptor site; Binding of the NMBA to the cholinoceptor; Processes initiated by the binding of the NMBA to the cholinoceptor, eventually resulting in neuromuscular block, i. e., pharmacodynamics.

A powerful tool in understanding the relationship between these processes and the time course of action of NMBAs is pharmacokinetic/pharmacodynamic (PK/PD) modelling [1] [2] [3]. By means of PK/PD analysis the pharmacokinetic behaviour (plasma concentration-time profile, and transport from plasma to the receptor site and vice versa), as well as the pharmacodynamic properties (relationship between the concentration at the receptor site - also called site of action, biophase, or effect compartment - and the effect) can be studied separately. PK/PD modelling and analysis have become essential tools in fundamental research on the factors governing the potency and time course of action of drugs, including the development of new NMBAs with a desired time course of action [4].

In this paper the onset time is defined as the time interval between administration and the time point of the peak effect in case of submaximal neuromuscular block (time to peak effect).

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Dr. Johannes H. Proost

Research Group for Experimental

Anaesthesiology and Clinical Pharmacology

Department of Anaesthesiology

University Hospital

Hanzeplein l

NL-9713 GZ Groningen

The Netherlands

Email: j.h.proost@farm.rug.nl