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Nifedipine is completely absorbed by the gastrointestinal tract and its pharmacokinetics and metabolism may be influenced by microorganisms. If gut microbes are involved in the metabolism of nifedipine, plateau hypoxia may regulate the bioavailability and the therapeutic effect of nifedipine by altering the metabolic activity of the gut microbiota. We herein demonstrated for the first time that gut flora is involved in the metabolism of nifedipine by in vitro experiments. In addition, based on the results of 16S rRNA analysis of feces in rats after acute plateau, we first confirmed that the plateau environment could cause changes in the number and composition of intestinal microbes. More importantly, these changes in flora could lead to a slower metabolic activity of nifedipine in the body after an acute plateau, resulting in increased bioavailability and therapeutic efficacy of nifedipine. Our research will provide basis and new ideas for changes in the fecal flora of human acutely entering the plateau, and contribute to rational drug use of nifedipine. [ABSTRACT FROM AUTHOR]

Some newest studies indicated that drug transports may play the key role in pharmacokinetics changes under hypoxia at high altitude; MDR1 is now known to affect the disposition of many administered drugs and make a major contribution to absorption, distribution, metabolism, excretion. Different expression of MDR1 is frequently found in different normal tissues and tumor cells; it is important to better understand how MDR1 is regulated under hypoxia, which seems to be a complex and highly controlled process. Several signaling pathways and transcription factors have been described as being involved in the regulation of MDR1 expression, such as MAPK/ERK, nuclear factor-kappaB, hypoxia-inducible factor-1a, pregnane × receptor, constitutive androstane receptor and microRNA. Recently, researches have been increasingly appreciating long non-coding RNAs (lncRNAs) as an integral component of gene regulatory networks. lncRNAs play crucial roles in various biological processes ranging from epigenetic gene regulation, transcriptional control, post-transcriptional regulation, pre-mRNA processing and nuclear organization. A last recent research showed that H19 gene non-coding RNA is believed to induce P-glycoprotein expression under hypoxia. [ABSTRACT FROM AUTHOR]