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British Journal of Anaesthesia, 2001, Vol. 86, No. 1 120-122
© 2001 The Board of Management and Trustees of the British Journal of Anaesthesia

Pharmacokinetic profile of epidurally administered methylnaltrexone, a novel peripheral opioid antagonist in a rabbit model

D. B. Murphy*,1, H. El Behiery1, V. W. Chan1 and J. F. Foss2

1Department of Anaesthesia, The Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada. 2Department of Anaesthesia and Critical Care, University of Chicago, Chicago IL, USA*Corresponding author: Department of Anaesthesia, Intensive Care and Pain Management,Cork University Hospital, Wilton, Cork City, Ireland

Methylnaltrexone (MNTX) is the first peripheral opioid receptor antagonist used in man to treat acute and chronic opiate-mediated side-effects. We describe in a rabbit model the pharmacokinetics of epidurally administered MNTX 0.66 mg kg–1, and we tested the hypothesis that epidurally administered MNTX does not penetrate the dura into the subarachnoid space. There were minimal concentrations of MNTX (40 ng ml–1) detected in the CSF at 10 and 20 min and none thereafter in comparison with the high serum levels. The serum drug concentration–time profile fitted a two-compartment pharmacokinetic model. Further studies are warranted as epidurally administered MNTX may have the potential to reverse epidural opioid-mediated side-effects whilst preserving analgesia.

Br J Anaesth 2001; 86: 120–2


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