TRITIATED NALTREXONE BINDING IN PLASMA FROM SEVERAL SPECIES AND TISSUE DISTRIBUTION IN MICE

Binding of 15,16-3H-naltrexone in human, monkey [Macaca mulatta], dog, guinea pig, rat and mouse plasma was investigated over a range of concentrations, including predicted therapeutic levels. In equilibrium dialysis studies at 37.degree. the extent of binding was independent of naltrexone concentration over the concentration range 1-500 ng/ml for dog plasma and 0.1-500 ng/ml for human, monkey, guinea pig, rat and mouse plasma. The extent of naltrexone binding in plasma is similar in the 6 species studied, the range being from 20% bound in rat plasma to 26% in plasma from beagle and mongrel dogs. This relatively low extent of naltrexone binding in plasma is consistent with previous findings of a large apparent volume of distribution for this drug in the dog. To investigate further the distribution of 3H-naltrexone, tissue levels of radioactivity in mice at 1, 5 and 15 min after i.v. administration of 8-3H-naltrexone were determined. Naltrexone was rapidly distributed from plasma to tissues, with less than 4% of the dose being present in plasma 1 min after injection.