A compartment model for subcutaneous injection of monoclonal antibodies.
Int J Pharm
; 650: 123687, 2024 Jan 25.
Article
em En
| MEDLINE
| ID: mdl-38103705
ABSTRACT
Despite the growing popularity of subcutaneous (SC) administration for monoclonal antibodies (mAbs), there remains a limited understanding of the significance of mAb transport rate constants within the interstitial space and the lymphatic system on their pharmacokinetics. To bridge this knowledge gap, we introduce a compartmental model for subcutaneously administered mAbs. Our model differentiates FcRn-expressing cells across various sites, and the model predictions agree with experimental data from both human and rat studies. Our findings indicate that the time to reach the maximum mAb concentration in the plasma, denoted by Tmax, displays a weak positive correlation with mAb half-life and a negligible correlation with bioavailability. In contrast, the half-life of mAbs exhibits a strong positive correlation with bioavailability. Moreover, the rate of mAb transport from lymph to plasma significantly affects the mAb half-life. Increasing the transport rates of mAbs from the injection site to the lymph or from lymph to plasma enhances bioavailability. These insights, combined with our compartmental model, contribute to a deeper understanding of the pharmacokinetics of subcutaneously administered mAbs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Modelos Epidemiológicos
/
Anticorpos Monoclonais
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos