Gutsy science: In vitro systems of the human intestine to model oral drug disposition.
Pharmacol Ther
; 230: 107962, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-34478775
ABSTRACT
The intestine has important gate-keeping functions that can profoundly affect the systemic blood exposure of orally administered drugs. Thus, characterizing a new molecular entity's (NME) disposition within the intestine is of utmost importance in drug development. While currently used in vitro systems, such as Ussing chamber, precision-cut intestinal slices, immortalized cell lines, and primary enterocytes provide substantial knowledge about drug absorption and the intestinal first-pass effect, they remain sub-optimal for quantitatively predicting this process and the oral bioavailability of many drugs. Use of novel in vitro systems such as intestinal organoids and intestinal microphysiological systems have provided substantial advances over the past decade, expanding our understanding of intestinal physiology, pathology, and development. However, application of these emerging in vitro systems in the pharmaceutical science is in its infancy. Preliminary work has demonstrated that these systems more accurately recapitulate the physiology and biochemistry of the intact intestine, as it relates to oral drug disposition, and thus they hold considerable promise as preclinical testing platforms of the future. Here we review currently used and emerging in vitro models of the human intestine employed in pharmaceutical science research. We also highlight aspects of these emerging tools that require further study.
Key words
Full text:
1
Collection:
01-internacional
Topics:
Acesso_medicamentos_insumos_estrategicos
Health context:
1_ASSA2030
Database:
MEDLINE
Main subject:
Gastrointestinal Tract
/
Intestines
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Pharmacol Ther
Year:
2022
Document type:
Article