Delayed clearance of morphine from the circulation of rabbits immunized with morphine-6-hemisuccinate bovine serum albumin.

Morphine clearance from the circulation of normal rabbits and rabbits with circulating anti-morphine antibody was studied. Individual animals were injected with 14C trace-labeled morphine in saline (6 mg morphine/kg body weight). The rabbits were bled at various times after morphine injection and the amount of morphine present in the serum at each time interval was determined. Morphine could be detected in the serum of normal animals for 1 week following injection and up to 12 weeks following injection in at least one animal with antibodies to morphine. The rate of morphine clearance in animals immunized to morphine-6-hemisuccinate-bovine serum albumin was not significantly different from normal during the first 4 hr after morphine injection. However, by 24 hr after injection, the rate of morphine clearance in morphine-6-hemisuccinate-bovine serum albumin-immunized animals was significantly slower than in normal animals. The amount of morphine present in the sera of the rabbits 24 hr after injection was related to the antigen-binding capacity and independent of antibody avidity. However, the rate of morphine clearance at times greater than 24 hr after injection was related to the average antibody avidity and not related to the antigen-binding capacity.