RT Journal Article
SR Electronic
T1 A recombinant humanized anti-cocaine monoclonal antibody alters the urinary clearance of cocaine and its metabolites in rats
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP dmd.118.083857
DO 10.1124/dmd.118.083857
A1 Jordan Marckel
A1 Hanna Wetzel
A1 Sihame Amlal
A1 Hassane Amlal
A1 Andrew Norman
YR 2018
UL http://dmd.aspetjournals.org/content/early/2018/12/21/dmd.118.083857.abstract
AB A recombinant humanized anti-cocaine monoclonal antibody, (h2E2), has shown potential in the preclinical phases for the treatment of cocaine abuse. The standard tests for cocaine usage are the detection of benzoylecgonine (BE) and cocaine in the urine. This includes workplace drug screens as well as in clinical trials for potential treatments of cocaine abuse. By sequestering cocaine into the plasma compartment, h2E2 prevents cocaine from entering the brain. Due to the altered disposition of cocaine in the presence of h2E2, we investigated the effects of h2E2 on cocaine and metabolite levels in the urine of rats to clarify the use of BE as an endpoint measurement for effectiveness in the future clinical trials. The urine concentration of cocaine and metabolites were considerably altered in the presence of h2E2. After a single injection of h2E2 (120 mg/kg) and cocaine HCl (0.56 mg/kg), the concentration of cocaine and BE excreted into the urine of rats decreased by 92% and 91% respectively from vehicle controls. Due to the significant decrease in urinary excretion, BE is not an appropriate indicator of cocaine usage in the presence of h2E2. Another endpoint measurement must be selected for the measurement of cocaine usage in the upcoming clinical trials of h2E2. In contrast to the effects on cocaine and BE urinary excretion, there was a 3-fold increase in ecgonine methyl ester (EME) the presence of h2E2. Therefore, we conclude that EME is a more appropriate measurement of cocaine intake in the presence of h2E2.