Sustained administration of cyclazocine for antagonism of morphine.

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 maintainat 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 drugs 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.