Preparation and evaluation of a sustained naloxone delivery system in rats

The use of a non-biodegradable polymer system to provide a sustained release of the narcotic antagonist naloxone in rats is described. The kinetics of morphine analgesia (measured by the hot-plate test) in the presence of the naloxone implant, and the urinary excretion of radiolabeled naloxone were measured. The shift of the morphine dose-response curve to the right is expressed in terms of dose ratios, which were calculated from the ED50 values for morphine obtained 9 days before, and 1, 8, 15, 22 and 29 days after implantation of the polymer. Our experiments indicate that effective levels of antagonist were maintained for 3-4 weeks after implantation of a polymer system containing 16 mg of naloxone. After 29 days, more than 95% of the absorbed drug had been released, with 16% of the implanted radioactivity appearing in the urine. These results demonstrate the feasibility of using a sustained release form of a narcotic antagonist to block the effects of morphine.