Repeated administration of a long acting mutant cocaine esterase: Effects on plasma cocaine levels and immune responses in rhesus monkeys

Previous studies in rhesus monkeys have described a dose‐dependent and rapid amelioration of the cardiovascular effects of cocaine by a long acting mutant cocaine esterase (T172R/G173Q; DM CocE). The current studies assessed the capacity of a relatively low dose of 0.32 mg/kg DM CocE to alter the pharmacokinetic profile of cocaine (3 mg/kg IV) in rhesus monkeys during four, bi‐weekly tests. The development of anti‐CocE antibodies was also assessed. During baseline conditions, cocaine exhibited a normal pharmacokinetic profile with plasma levels of >2000 ng/ml observed 15 min after cocaine, and an elimination half‐life of approximately 45 min. When administered either immediately, or 10 min after cocaine, 0.32 mg/kg DM CocE resulted in a rapid elimination of cocaine, with plasma levels below detection limits within the first 5 to 8 min after administration during each of the four tests. Although slight (10‐fold) increases in anti‐CocE antibody titer was observed prior to the fourth test, these antibodies did not appear to be neutralizing, and dissipated within seven weeks. These results suggest that DM CocE may provide a novel, and effective therapeutic for the treatment of acute cocaine toxicity.