The effects of a humanized anti-cocaine monoclonal fab fragment on the urinary excretion of cocaine and metabolites

Abstract

By Mackenzie Turner, Biology

Advisor: Andrew Norman

Presentation ID: PM_A29

Abstract: Cocaine abuse, addiction, and dependence are major threats to world health. Currently, there are no approved medications for cocaine abuse. The anti-cocaine monoclonal antibody h2E2 prevents cocaine from crossing the blood-brain barrier by sequestering it in the plasma. h2E2 will enter clinical trials in 2019. Studies have suggested that the purified Fab binding portion of h2E2 might mimic the sequestering ability of h2E2. The Fab fragment clears faster and accelerates the urinary clearance of cocaine; therefore, it may be a favorable candidate for clinical treatment of cocaine use disorders. Since cocaine and cocaine metabolite concentrations in the urine are used as a measure of efficacy in clinical trials, the effects of the Fab fragment on the urinary profile of cocaine was investigated. 11 adult male rats were individually placed in metabolic cages. A baseline urine output was established, collecting every 3 hours for 24 hours. Fab fragment (83 mg/kg) or vehicle was infused intravenously. One hour post-infusion, an equimolar dose of cocaine HCl (0.56 mg/kg) was injected. Urine was collected every 3 hours for 24 hours. Food and water intake were measured and unaffected by either treatment. Creatinine excretion levels in urine were quantified and unchanged by the treatments. Fab caused a two-fold increase in urinary clearance of cocaine, as measured by LC-MS. In conclusion, the Fab fragment alters the metabolism and excretion of cocaine in rats, indicating that the Fab fragment may be beneficial for treating cocaine overdose or toxicity.