The Influences and Mechanisms of High-altitude Hypoxia Exposure on Drug Metabolism.
Curr Drug Metab
; 24(3): 152-161, 2023.
Article
en En
| MEDLINE
| ID: mdl-36579391
BACKGROUND: The special environment of high-altitude hypoxia not only changes the physiological state of the body but also affects the metabolic process of many drugs, which may affect the safety and efficacy of these drugs. The number of drugs is huge, so it is not wise to blindly repeat the pharmacokinetic studies of all of them on the plateau. Mastering the law of drug metabolism on the plateau is conducive to the comprehensive development of rational drug use on the plateau. Therefore, it is very important to determine the impacts and elucidate the mechanism of drug metabolism in hypobaric hypoxia conditions. METHODS: In this review, we searched published studies on changes in drug metabolism in hypoxia conditions to summarize and analyze the mechanisms by which hypoxia alters drug metabolism. RESULTS: Although the reported effects of high-altitude hypoxia on drug metabolism are sometimes controversial, metabolism kinetics for most of the tested drugs are found to be affected. Mechanism studies showed that the major reasons causing metabolism changes are: regulated drug-metabolizing enzymes expression and activity mediated by HIF-1, nuclear receptors and inflammatory cytokines, and change in direct or indirect effects of intestinal microflora on drug metabolism by itself or the host mediated by microflora-derived drug-metabolizing enzymes, metabolites, and immunoregulation. CONCLUSION: Altered enzyme expression and activity in the liver and altered intestinal microflora are the two major reasons to cause altered drug metabolism in hypoxia conditions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mal de Altura
/
Microbioma Gastrointestinal
Límite:
Humans
Idioma:
En
Revista:
Curr Drug Metab
Asunto de la revista:
METABOLISMO
/
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos