Sustained administration of cyclazocine for antagonism of morphine

• Published in: Drug and alcohol dependence Vol. 1; no. 6; pp. 415 - 428
• Main Authors: Sullivan, M.F., Ruemmler, P.S., Kalkwarf, D.R.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.10.1976
• Subjects: Animals; Bile - analysis; Cyclazocine - administration & dosage; Cyclazocine - metabolism; Cyclazocine - pharmacology; Drug Implants; Duodenum - metabolism; Feces - analysis; Female; Humans; Infusions, Parenteral; Injections, Subcutaneous; Morphine - antagonists & inhibitors; Morphine Dependence - metabolism; Rabbits; Rats
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/0376-8716(76)90006-5

The plasma levels, distribution and excretion of tritium were determined after administration of a single or sustained dose of 3H-cyclazocine to naive and morphine-addicted rats. The plasma levels reached and maintained in the naive animals were higher than those in addicted rats, suggesting that animals tolerant to morphine were cross-tolerant to cyclazocine. Although only half the administered radioactivity was excreted after either a single dose or a continuous administration, no appreciable concentration was found in any of the organs studied. The behavior of a single or sustained dose of cyclazocine was also determined in rabbits to evaluate the effect of the implant site on the drug release rate and tissue biocompatibility. The release-rate of 3H-cyclazocine from a glyceride matrix implanted subcutaneously or intramuscularly could be controlled by modification of the matrix itself or by manipulation of the drug concentration within the matrix. Durations of action between a few days and a month were obtained by these means from devices that were both biodegradable and tissue compatible. The results indicate that the procedures used here may provide a practical means for administering narcotic antagonists to addicts.