Clinical pharmacokinetics of cholinesterase inhibitors

Clin Pharmacokinet. 1986 May-Jun;11(3):236-49. doi: 10.2165/00003088-198611030-00005.


This review deals mainly with the pharmacokinetics of the reversible quaternary cholinesterase inhibitors neostigmine, pyridostigmine and edrophonium, which are mainly used to antagonise non-depolarising neuromuscular blockade in general anaesthesia and in the symptomatic treatment of myasthenia gravis. Only in the last few years, since the introduction of highly sensitive and selective analytical procedures based on gas and liquid chromatography, have proper pharmacokinetic studies of these drugs become possible. Rapid cooling and addition of internal standard to samples before freezing are important precautions in view of the poor stability of the cholinesterase inhibitors in plasma and blood. Plasma clearances of the reversible quaternary cholinesterase inhibitors are in the range 0.5 to 1.0 L/h/kg and their apparent volumes of distribution range from 0.5 to 1.7 L/kg. Accordingly, the drugs have short plasma elimination half-lives, in the order of 30 to 90 minutes. One to two hours after oral administration of 60 mg pyridostigmine, peak plasma concentrations of 40 to 60 micrograms/L are observed, whereas the plasma concentrations of neostigmine after a 30 mg oral dose are only 1 to 5 micrograms/L. The oral bioavailability of these hydrophilic ionised compounds is low: that of pyridostigmine is approximately 10% and the value for neostigmine is even lower. In spite of the short elimination half-life of pyridostigmine, intraindividual variations in plasma concentration during a dose interval are small in myasthenic patients receiving oral maintenance therapy, probably as a result of slow absorption from the gastrointestinal tract. Severely impaired renal function has been shown to prolong the elimination of neostigmine and pyridostigmine, while methylcellulose has been reported to inhibit the absorption of the latter drug completely. Other pharmacokinetic drug interactions suggested so far do not seem to be of clinical significance. Although a positive correlation has been demonstrated between the plasma concentrations of these drugs and their pharmacological effects as measured by a decrement in muscle response to repetitive nerve stimulation in a single muscle, this relationship is less clear when a global evaluation of muscular function in myasthenia gravis is used. Pharmacokinetic studies of the tertiary reversible cholinesterase inhibitor physostigmine, an important tool in experimental cholinergic neuropharmacology, are still in their initial stages. This drug too is characterised by a short plasma elimination half-life of 20 to 30 minutes.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / pharmacology
  • Adult
  • Aging
  • Animals
  • Biological Availability
  • Child
  • Cholinesterase Inhibitors / metabolism*
  • Cholinesterase Inhibitors / therapeutic use
  • Drug Interactions
  • Edrophonium / metabolism
  • Humans
  • Infant
  • Kidney Diseases / metabolism
  • Kinetics
  • Middle Aged
  • Myasthenia Gravis / metabolism
  • Neostigmine / metabolism
  • Ophthalmic Solutions
  • Physostigmine / metabolism
  • Pyridostigmine Bromide / metabolism
  • Trichlorfon / metabolism


  • Adrenal Cortex Hormones
  • Cholinesterase Inhibitors
  • Ophthalmic Solutions
  • Neostigmine
  • Edrophonium
  • Physostigmine
  • Trichlorfon
  • Pyridostigmine Bromide