Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity
| Autor: | Rose P. Webster, Jordan A. Marckel, Andrew B. Norman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Human Vaccines & Immunotherapeutics, Vol 19, Iss 3 (2023) |
| Druh dokumentu: | article |
| ISSN: | 21645515 2164-554X 2164-5515 |
| DOI: | 10.1080/21645515.2023.2274222 |
| Popis: | ABSTRACTA 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. |
| Databáze: | Directory of Open Access Journals |
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