The effects of a monoclonal anti-cocaine fab fragment on urinary excretion of cocaine in rats
Start Date
29-4-2022 3:45 PM
Location
Alter Hall Poster Session 2 - 2nd floor
Abstract
Despite overdose deaths in the US being on the rise, there is still no FDA approved pharmacological treatment for cocaine use disorder. A novel anti-cocaine recombinant humanized monoclonal antibody (mAb), designated h2E2, is at an advanced stage of preclinical development for the treatment of cocaine use disorder. In previous studies, h2E2 has been found to be too large to effectively be cleared from the blood via the kidneys. As almost all drug tests are performed using urine samples, there is concern that the drug would suppress urinary clearance of cocaine, causing a patient to falsely test negative for cocaine usage. To improve urinary excretion, a fragment of the h2E2 antibody was synthesized. The fragment contains only the variable region, called the Fab fragment. Fab binds to cocaine using the same mechanism as h2E2 but should be small enough to clear in the urine. Creatinine is a normal metabolic by-product and is a good indication of kidney filtration. Therefore, we collected urine from rats treated with cocaine and the fab fragment and quantified Fab and creatinine levels. In the presence of cocaine, we observed higher Fab excretion rates in the urine at early timepoints, but by 12 hours the same amount of Fab had been excreted. Additionally, creatinine concentrations were higher in the cocaine treated animals at the early timepoint, but lower by 6 hours. This indicates that the altered Fab excretion observed in the presence of cocaine was likely due to overall higher filtration rates at the early timepoints as compared to the vehicle control. Overall, we demonstrated the Fab is excreted in the urine in rats. Cocaine does not appear to have a specific effect on fab excretions rates. However, Fab may alter filtration rates. More work is needed to fully understand the interaction between the h2E2 Fab fragment and cocaine and their effects on excretion of these compounds in to the urine.
The effects of a monoclonal anti-cocaine fab fragment on urinary excretion of cocaine in rats
Alter Hall Poster Session 2 - 2nd floor
Despite overdose deaths in the US being on the rise, there is still no FDA approved pharmacological treatment for cocaine use disorder. A novel anti-cocaine recombinant humanized monoclonal antibody (mAb), designated h2E2, is at an advanced stage of preclinical development for the treatment of cocaine use disorder. In previous studies, h2E2 has been found to be too large to effectively be cleared from the blood via the kidneys. As almost all drug tests are performed using urine samples, there is concern that the drug would suppress urinary clearance of cocaine, causing a patient to falsely test negative for cocaine usage. To improve urinary excretion, a fragment of the h2E2 antibody was synthesized. The fragment contains only the variable region, called the Fab fragment. Fab binds to cocaine using the same mechanism as h2E2 but should be small enough to clear in the urine. Creatinine is a normal metabolic by-product and is a good indication of kidney filtration. Therefore, we collected urine from rats treated with cocaine and the fab fragment and quantified Fab and creatinine levels. In the presence of cocaine, we observed higher Fab excretion rates in the urine at early timepoints, but by 12 hours the same amount of Fab had been excreted. Additionally, creatinine concentrations were higher in the cocaine treated animals at the early timepoint, but lower by 6 hours. This indicates that the altered Fab excretion observed in the presence of cocaine was likely due to overall higher filtration rates at the early timepoints as compared to the vehicle control. Overall, we demonstrated the Fab is excreted in the urine in rats. Cocaine does not appear to have a specific effect on fab excretions rates. However, Fab may alter filtration rates. More work is needed to fully understand the interaction between the h2E2 Fab fragment and cocaine and their effects on excretion of these compounds in to the urine.
