Cetuximab Exhibits Sex Differences in Lymphatic Exposure after Intravenous Administration in Rats in the Absence of Differences in Plasma Exposure.
Pharm Res
; 37(11): 224, 2020 Oct 19.
Article
em En
| MEDLINE
| ID: mdl-33078255
ABSTRACT
PURPOSE:
The aim of this work was to identify whether biochemical and physiological sources of mAb pharmacokinetic sex-effects could be identified in the rat model where target-mediated disposition is avoided.METHODS:
Plasma and lymphatic pharmacokinetics of the humanised anti-EGFR antibody cetuximab, along with potential physiological and biochemical drivers of pharmacokinetic sex differences, were examined in male and female rats. Cetuximab was used as a model mAb since plasma clearance is slower in female patients.RESULTS:
When plasma concentrations were normalised to dose, female rats displayed slower plasma clearance than males, but no significant differences were observed in liver and spleen biodistribution. Sex differences in apparent plasma clearance, however, were abolished after normalisation to body weight, surface area or fat-free mass. Significant sex differences were observed in plasma testosterone, endogenous IgG and fat free mass, but did not correlate with apparent clearance. Females did, however, show two-fold higher lymphatic exposure compared to males.CONCLUSIONS:
These data suggested that mAbs more efficiently access lymph in females, but this does not affect plasma pharmacokinetics or biodistribution. Further, the data suggest that sex differences observed in humans could be a function of antigen density.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Cetuximab
/
Antineoplásicos Imunológicos
/
Sistema Linfático
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Austrália