Pharmacokinetic profile of epidurally administered methylnaltrexone, a novel peripheral opioid antagonist in a rabbit model.
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.
Murph
D B
DB
Department of Anaesthesia, The Toronto Western Hospital and University of Toronto, Ontario, Canada.
El Behiery
H
H
Chan
V W
VW
Foss
J F
JF
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
D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone