Tritiated Naltrexone Binding in Plasma from Several Species and Tissue Distribution in Mice

• Published in: Journal of pharmaceutical sciences 1976-05, Vol.65 (5), p.712-716
• Main Authors: Ludden, T.M., Malspeis, L., Baggot, J.D., Sokoloski, T.D., Frank, S.G., Reuning, R.H.
• Format: Article
• Language: English
• Subjects: and mice; Animals; Antagonists; Antagonists, narcotic—naltrexone, pharmacokinetics, humans, monkeys, dogs, guinea pigs, rats, and mice; Distribution; Distribution, tissue—naltrexone, mice; Dogs; Female; Guinea Pigs; Haplorhini; Humans; Macaca mulatta; Male; Mice; monkeys; Naloxone - analogs & derivatives; Naltrexone - blood; Naltrexone - metabolism; Naltrexone-plasma protein binding in humans; Naltrexone—plasma protein binding in humans, monkeys, dogs, guinea pigs, rats, and mice, tissue distribution in mice; narcotic-naltrexone; pharmacokinetics; Pharmacokinetics-naltrexone; Pharmacokinetics—naltrexone, humans, monkeys, dogs, guinea pigs, rats, and mice; plasma-naltrexone; Protein binding; Protein binding, plasma—naltrexone, humans, monkeys, dogs, guinea pigs, rats, and mice; Rats; Species Specificity; Time Factors; tissue distribution in mice; tissue-naltrexone
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600650521

The binding of 15,16‐3H‐naltrexone in human, monkey, dog, guinea pig, rat, and mouse plasma was investigated over a range of concentrations, including predicted therapeutic levels. Studies using equilibrium dialysis at 37° indicate that the extent of binding is independent of naltrexone concentration over the concentration range of 1–500 ng/ml for dog plasma and of 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 six 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 tritiated naltrexone, the tissue levels of radioactivity in mice at 1, 5, and 15 min after intravenous 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 at 1 min after injection.