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The Effects of a Humanized Anti‐Cocaine Monoclonal Antibody on Cocaine Metabolism and Urinary Excretion in Mice
Author(s) -
Wetzel Hanna,
Tabet Michael,
Norman Andrew
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.930.2
Subject(s) - metabolite , urine , excretion , benzoylecgonine , metabolism , chemistry , pharmacokinetics , pharmacology , urinary system , monoclonal antibody , endocrinology , medicine , antibody , immunology , biochemistry
The humanized recombinant anti‐cocaine monoclonal antibody h2E2 is a potential immunotherapy for cocaine abuse. h2E2 may be expected to inhibit the metabolism of cocaine, yet over one hour it had no effect on cocaine's elimination rate. It was hypothesized that this apparent elimination represents a slowed distribution. The effects of h2E2 on cocaine metabolism and excretion over 6 hours were investigated. Mice were injected with h2E2 or vehicle, then one hour later with an equimolar dose of cocaine. At times ranging from 45 s to 6 h, mice were sacrificed and blood was collected. Urine was collected from the time of cocaine injection until animals were sacrificed. GC/MS was used to quantify cocaine and its major metabolite in mice, ecgonine methyl ester (EME). In vehicle and h2E2 treated mice, after the initial one‐hour decline plasma cocaine concentrations were steady, though at levels 2.8‐fold higher in h2E2 treated mice. In vehicle treated mice, EME formation was complete within the first hour, then declined with a 57 min half‐life. EME plasma concentrations were lower in the presence of h2E2 over the first hour, and undetectable thereafter. This indicates that the metabolism of cocaine was inhibited by h2E2. Cocaine and EME concentrations were 89 and 50% lower in the urine of mice treated with h2E2, indicating that h2E2 also inhibited urinary excretion of cocaine. As there is no evidence that cocaine is being metabolized or excreted, it is likely that the disappearance of cocaine from the plasma represents distribution into a non‐plasma compartment, or a change in the metabolic pathway. Despite these dramatic effects, how cocaine is eliminated from the body in the presence of h2E2 remains to be elucidated. Supported by NIH DP1DA031386.