Direct bioanalysis or indirect calculation of target engagement and free drug exposure: do we apply double standards?
Bioanalysis
; 15(1): 5-16, 2023 Jan.
Article
en En
| MEDLINE
| ID: mdl-36762451
Analysis of "free" drug/target concentrations is important to set up appropriate pharmacokinetic-pharmacodynamic models, to evaluate active-drug exposure and target engagement. Such "free-analyte" determination could be done by direct bioanalysis using an appropriate "free-analyte" assay. Development of "free" assays is often considered challenging from a technological and regulatory perspective. The application of a "total-total" approach, where the "free-analyte" concentration is determined mathematically, is considered a more convenient option. In this perspective, we examine and discuss the challenges of this "total-total" approach, from the affinity data, the importance of applying an appropriate "total" assay, the impact of additional binding partners and the variability of the total drug/target assays and their impact on the quality and variability of the final "free-analyte" dataset.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Farmacocinética
/
Preparaciones Farmacéuticas
Idioma:
En
Revista:
Bioanalysis
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido