Pharmacokinetics and pharmacodynamics of antibody-drug conjugates for the treatment of patients with breast cancer.
Expert Opin Drug Metab Toxicol
; 20(1-2): 45-59, 2024.
Article
en En
| MEDLINE
| ID: mdl-38214896
ABSTRACT
INTRODUCTION:
Currently three antibody-drug-conjugates (ADC) are approved by the European Medicines Agency (EMA) for treatment of breast cancer (BC) patient trastuzumab-emtansine, trastuzumab-deruxtecan and sacituzumab-govitecan. ADC are composed of a monoclonal antibody (mAb) targeting a specific antigen, a cytotoxic payload and a linker. Pharmacokinetics (PK) and pharmacodynamics (PD) distinguish ADC from conventional chemotherapy and must be understood by clinicians. AREAS COVERED Our review delineates the PK/PD profiles of ADC approved for the treatment of BC with insight for future development. This is an expert opinion literature review based on the EMA's Assessment Reports, enriched by a comprehensive literature search performed on Medline in August 2023. EXPERT OPINION All three ADC distributions are described by a two-compartment structure tissue and serum. Payload concentration peak is immediate but remains at low concentration. The distribution varied for all ADC only with body weight. mAb will be metabolised firstly by the saturable complex formation of ADC/Tumour-Receptor and secondly by binding of FcgRs in immune cells. They are all excreted in the bile and faeces with minimal urine elimination. Dose adjustments, apart from weight, are not recommended. Novel ADC are composed of cleavable linkers with various targets/payloads with the same PK/PD properties, but novel structures of ADC are in development.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
Problema de salud:
1_medicamentos_vacinas_tecnologias
Asunto principal:
Neoplasias de la Mama
/
Inmunoconjugados
/
Antineoplásicos
Límite:
Female
/
Humans
Idioma:
En
Revista:
Expert Opin Drug Metab Toxicol
Asunto de la revista:
METABOLISMO
/
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Bélgica