Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity
A humanized monoclonal antibody h2E2 designed to bind cocaine with high affinity, specificity, and a long half-life (~7 d in rats) is being developed as a treatment for cocaine use disorder. We report here a pharmacokinetic (PK) study of h2E2 using male and female rats conducted under a Good Laborat...
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Taylor & Francis Group
2023-12-01
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| Series: | Human Vaccines & Immunotherapeutics |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21645515.2023.2274222 |
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| author | Rose P. Webster Jordan A. Marckel Andrew B. Norman |
| author_facet | Rose P. Webster Jordan A. Marckel Andrew B. Norman |
| author_sort | Rose P. Webster |
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| description | A humanized monoclonal antibody h2E2 designed to bind cocaine with high affinity, specificity, and a long half-life (~7 d in rats) is being developed as a treatment for cocaine use disorder. We report here a pharmacokinetic (PK) study of h2E2 using male and female rats conducted under a Good Laboratory Practice (GLP) protocol over a dose range of 40 to 1200 mg/kg. The maximum concentration measured in rat plasma (Cmax) varied proportionately to the dose administered in both male and female rats. The terminal elimination half-lives (t1/2β) were not significantly different in male and female rats at all doses tested. Importantly, this study reports pharmacokinetics for a humanized monoclonal antibody at a dose never tested before. h2E2 has a high affinity for cocaine, whereas low or no affinity was demonstrated for cocaine metabolites (all except cocaethylene), endogenous monoamines, and methamphetamine. This demonstrates its specificity and a potential lack of interactions with physiological and endocrine systems. A review of the clinical signs in single-dose toxicity studies in rats revealed no effects on the central nervous, respiratory, or cardiovascular systems following single intravenous doses of 40 to 1200 mg/kg. This study predicts that this monoclonal antibody may be safe and effective in humans. |
| format | Article |
| id | doaj-art-11df4beb242d4c0db3e7dcfdfd587cab |
| institution | OA Journals |
| issn | 2164-5515 2164-554X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
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| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj-art-11df4beb242d4c0db3e7dcfdfd587cab2025-08-20T02:31:56ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2023-12-0119310.1080/21645515.2023.2274222Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivityRose P. Webster0Jordan A. Marckel1Andrew B. Norman2Department of Pharmacology & Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH, USADepartment of Pharmacology & Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH, USADepartment of Pharmacology & Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH, USAA humanized monoclonal antibody h2E2 designed to bind cocaine with high affinity, specificity, and a long half-life (~7 d in rats) is being developed as a treatment for cocaine use disorder. We report here a pharmacokinetic (PK) study of h2E2 using male and female rats conducted under a Good Laboratory Practice (GLP) protocol over a dose range of 40 to 1200 mg/kg. The maximum concentration measured in rat plasma (Cmax) varied proportionately to the dose administered in both male and female rats. The terminal elimination half-lives (t1/2β) were not significantly different in male and female rats at all doses tested. Importantly, this study reports pharmacokinetics for a humanized monoclonal antibody at a dose never tested before. h2E2 has a high affinity for cocaine, whereas low or no affinity was demonstrated for cocaine metabolites (all except cocaethylene), endogenous monoamines, and methamphetamine. This demonstrates its specificity and a potential lack of interactions with physiological and endocrine systems. A review of the clinical signs in single-dose toxicity studies in rats revealed no effects on the central nervous, respiratory, or cardiovascular systems following single intravenous doses of 40 to 1200 mg/kg. This study predicts that this monoclonal antibody may be safe and effective in humans.https://www.tandfonline.com/doi/10.1080/21645515.2023.2274222Cocaine addictionhumanizedh2E2monoclonal antibodypharmacokineticstoxicokinetics |
| spellingShingle | Rose P. Webster Jordan A. Marckel Andrew B. Norman Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity Human Vaccines & Immunotherapeutics Cocaine addiction humanized h2E2 monoclonal antibody pharmacokinetics toxicokinetics |
| title | Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity |
| title_full | Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity |
| title_fullStr | Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity |
| title_full_unstemmed | Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity |
| title_short | Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity |
| title_sort | toxicokinetics of a humanized anti cocaine monoclonal antibody in male and female rats and lack of cross reactivity |
| topic | Cocaine addiction humanized h2E2 monoclonal antibody pharmacokinetics toxicokinetics |
| url | https://www.tandfonline.com/doi/10.1080/21645515.2023.2274222 |
| work_keys_str_mv | AT rosepwebster toxicokineticsofahumanizedanticocainemonoclonalantibodyinmaleandfemaleratsandlackofcrossreactivity AT jordanamarckel toxicokineticsofahumanizedanticocainemonoclonalantibodyinmaleandfemaleratsandlackofcrossreactivity AT andrewbnorman toxicokineticsofahumanizedanticocainemonoclonalantibodyinmaleandfemaleratsandlackofcrossreactivity |