Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity.
Hum Vaccin Immunother
; 19(3): 2274222, 2023 12 15.
Article
em En
| MEDLINE
| ID: mdl-37936497
ABSTRACT
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 (t1/2ß) 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cocaína
/
Anticorpos Monoclonais Humanizados
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article