Pharmacokinetic/pharmacodynamic modeling of rocuronium in myasthenic patients is improved by taking into account the number of unbound acetylcholine receptors

A De Haes*, JH Proost, JBM Kuks, DC van den Tol, JMKH Wierda

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)


Patients with myasthenia gravis are more sensitive than healthy patients to nondepolarizing neuromuscular blocking drugs. We performed a pharmacokinetic/pharmacodynamic modeling study of rocuronium in eight myasthenic patients and eight matched control patients. Patients were anesthetized with propofol and sufentanil and a mixture of nitrous oxide/oxygen. Mechanomyographical monitoring of the adductor pollicis was applied. Rocuronium was infused at a rate of 25 mug . kg(-1) . min(-1) in myasthenic patients and 116.7 mug . kg(-1) . min(-1) in control patients and was terminated at 70% neuromuscular block. Arterial blood samples were drawn during onset and offset of the block and for 4 h after the administration of rocuronium. Plasma concentrations were determined by high-performance liquid chromatography. Pharmacokinetic/pharmacodynamic modeling was performed by using the Sheiner model and the unbound receptor model (URM), which takes into account the number of unbound acetylcholine receptors. The effective concentration at 50% effect and the steepness of the concentration-effect relationship were significantly decreased in myasthenic patients. Both the URM and the Sheiner model provided an adequate fit in myasthenic patients. The acetylcholine receptor concentration was significantly decreased in myasthenic patients. The URM explains the observed differences in time course and potency, whereas the Sheiner model does not.

Original languageEnglish
Pages (from-to)588-596
Number of pages9
JournalAnesthesia and Analgesia
Issue number3
Publication statusPublished - Sept-2002


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