The chimeric human/mouse anti-
cocaine monoclonal antibody (mAb) 2E2 and its further humanized variant h2E2 have been reported to sequester a significant portion of
cocaine in plasma and decrease
cocaine concentrations in the brain in mice and rats. However, many
cocaine users co-
abuse alcohol, leading to the formation of the centrally active metabolite
cocaethylene. This potentially compromises the efficacy of a
cocaine-specific
immunotherapy. Because h2E2 has high affinity for
cocaethylene as well as
cocaine, the ability of h2E2 to prevent
cocaethylene entry into the brain was investigated. Mice were infused with h2E2 (1.6 μmol/kg i.v.) or vehicle and after one hour were injected with
cocaethylene fumarate (1.2 μmol/kg i.v.). At times from 45 s to 60 min, brain and plasma were collected and
cocaethylene concentrations were measured using GC/MS. In control mice, a two-compartment pharmacokinetic model generated values for
cocaethylene distribution and terminal elimination half-lives of 0.5 and 8.1 min respectively. Initial plasma
cocaethylene concentrations increased 13-fold from controls in the presence of h2E2. In brain, h2E2 produced a 92% decrease in the area under the time-concentration curve for
cocaethylene. The pharmacokinetics of h2E2 was also characterized in detail. A three-compartment model resolved an initial distribution half-life of 4.4 min and a second distribution half-life of 4.2 h, and a terminal elimination half-life of 7.8 days. The ability of h2E2 to protect the brain from both
cocaine and
cocaethylene predicts that the clinical efficacy of h2E2 will be retained in
cocaine users who co-
abuse alcohol.