Abstract
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.
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