ArticleDrug metabolism and disposition: the biological fate of chemicals2019
A Recombinant Humanized Anticocaine Monoclonal Antibody Alters the Urinary Clearance of Cocaine and Its Metabolites in Rats.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- A humanized anti-cocaine mAb antagonizes the cardiovascular effects of cocaine in rats.Pharmacology research & perspectives · 2023Article
- Structures of drug-specific monoclonal antibodies bound to opioids and nicotine reveal a common mode of binding.Structure (London, England : 1993) · 2023Article
- Effects of a recombinant humanized anti-cocaine monoclonal antibody on the metabolism and distribution of cocaine in vitro and in mice.Pharmacology research & perspectives · 2022Review
- Pharmacological Profiling of Antifentanyl Monoclonal Antibodies in Combination with Naloxone in Pre- and Postexposure Models of Fentanyl Toxicity.The Journal of pharmacology and experimental therapeutics · 2022Article
- Monoclonal Antibodies Counteract Opioid-Induced Behavioral and Toxic Effects in Mice and Rats.The Journal of pharmacology and experimental therapeutics · 2020Article
- A novel differential scanning fluorimetry analysis of a humanized anti-cocaine mAb and its ligand binding characteristics.Journal of immunological methods · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A recombinant humanized anticocaine 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 future clinical trials. The urine concentrations of cocaine and metabolites were considerably altered in the presence of h2E2. After a single injection of h2E2 (120 mg/kg) and cocaine hydrochloride (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) in the presence of h2E2. Therefore, we conclude that EME is a more appropriate measurement of cocaine intake in the presence of h2E2.
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