Evaluation of critical parameters in the hollow-fibre system for tuberculosis: A case study of moxifloxacin.
Br J Clin Pharmacol
; 90(7): 1711-1727, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38632083
RESUMEN
AIMS:
The hollowfibre system for tuberculosis (HFSTB) is a preclinical model qualified by the European Medicines Agency to underpin the antiTB drug development process. It can mimic in vivo pharmacokinetic (PK)pharmacodynamic (PD) attributes of selected antimicrobials, which could feed into in silico models to inform the design of clinical trials. However, historical data and published protocols are insufficient and omit key information to allow experiments to be reproducible. Therefore, in this work, we aim to optimize and standardize various HFSTB operational procedures.METHODS:
First, we characterized bacterial growth dynamics with different types of hollowfibre cartridges, Mycobacterium tuberculosis strains and media. Second, we mimicked a moxifloxacin PK profile within hollowfibre cartridges, in order to check drugfibres compatibility. Lastly, we mimicked the moxifloxacin total plasma PK profile in human after once daily oral dose of 400 mg to assess PKPD after different sampling methods, strains, cartridge size and bacterial adaptation periods before drug infusion into the system.RESULTS:
We found that final bacterial load inside the HFSTB was contingent on the studied variables. Besides, we demonstrated that drugfibres compatibility tests are critical preliminary HFSTB assays, which need to be properly reported. Lastly, we uncovered that the sampling method and bacterial adaptation period before drug infusion significantly impact actual experimental conclusions.CONCLUSION:
Our data contribute to the necessary standardization of HFSTB experiments, draw attention to multiple aspects of this preclinical model that should be considered when reporting novel results and warn about critical parameters in the HFSTB currently overlooked.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Moxifloxacino
/
Mycobacterium tuberculosis
/
Antituberculosos
Límite:
Humans
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Reino Unido