title: Pharmacokinetic profile of epidurally administered methylnaltrexone, a novel peripheral opioid antagonist in a rabbit model.
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.
authors.affiliation: Department of Anaesthesia, The Toronto Western Hospital and University of Toronto, Ontario, Canada.
authors.forename: D B
authors.initials: DB
authors.lastname: Murph
authors.forename: H
authors.initials: H
authors.lastname: El Behiery
authors.forename: V W
authors.initials: VW
authors.lastname: Chan
authors.forename: J F
authors.initials: JF
authors.lastname: Foss
mesh_terms: D000818:Animals; D007268:Injections, Epidural; D023421:Models, Animal; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D009292:Narcotic Antagonists / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D000644:Quaternary Ammonium Compounds; D011817:Rabbits
chemical_list: D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone