Duration of human MU opiate receptor blockade following naltrexone: Measurement by 11C‐carfentanil pet

Background Naltrexone is a mu opiate receptor antagonist approved for the treatment of alcohol dependency. Previous reports have suggested a duration of receptor occupancy of naltrexone that greatly exceeds that predicted by it's 4 hour T1/2, or the 13 hour T1/2 of beta naltrexol, the predominant metabolite. We undertook a double blind, placebo controlled, randomized study of receptor occupancy using the highly selective mu opiate receptor ligand 11C‐carfentanil. Methods Healthy volunteers underwent PET imaging with 11C‐carfentanil at baseline, 3 24, 72 and 144 hours following a single dose of placebo, 12.5, 50 or 100mg of naltrexone. Regional analysis was undertaken using a statistical parametric mapping approach (SPM2). Results To date, 15 of 24 subjects have completed all phases of the study. At interim analysis, regions of significantly (p<0.001) lower activity were mapped in all known regions of brain mu receptors 3 and 24 hours following all doses of naltrexone. This effect was measurable at 72 hours for the combined 50/100mg dose. At 144 hours, significant blockade remained in the left temporal lobe. (see Table) Conclusions Our findings provide tomographic evidence of a persistence of blockade of the mu opiate receptor for up to 144 hours following naltrexone, with no evidence of a receptor level placebo effect. Correlation with plasma naltrexone and beta naltrexone is planned. Clinical Pharmacology & Therapeutics (2005) 77 , P26–P26; doi: 10.1016/j.clpt.2004.11.099Placebo 12.5 mg 50/100 mgBaseline vs N = 6 N = 4 N = 5 3H NS P < 0.001 P < 0.001 24H NS P < 0.001 P < 0.001 72H NS NS P < 0.001 144H NS NS P < 0.01