Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine

Abstract

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.

Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes

“…Hence, the diet greatly influences the diversity of the microbiota in the gut (Table 1). The microbiota is genetically well equipped to utilize various nutritional substrates [68] and maintains the normal gut microbiota pattern. A recent study has also shown that an increase in fat consumption generates a more gram-positive/gram-negative index of the gut microbiota [8].…”

Effects of intestinal flora on the pharmacokinetics and pharmacodynamics of aspirin in high-altitude hypoxia

“…Fecal samples were sent to the BGI gene for 16S rRNA analysis in order to discover alterations in intestinal flora after rapidly ascent to high altitude. Cetyltrimethyl Ammonium Bromide (CTAB) method for extracting genomic DNA from fecal samples, followed by PCR analysis immediately [5]. We conducted bioinformatics analysis on qualified samples.…”

“…Aspirin and salicylic acid concentrations were analyzed using UFLC-MS / MS. High performance liquid chromatography (UFLC-20A, Shimadzu Corporation, Japan); Shim-pack XR-ODS column; Triple quadrupole mass spectrometer (API3200, Applied Biosystems, USA). The atomization temperature was 250˚C and the flow rate is 0.4 mL/min [5]. Electrospray ionization assay was used for in vitro incubation concentration of remaining aspirin and plasma concentration of salicylic acid in vivo.…”

“…Consequently, any alteration or dysbiosis of the gut microbiota could directly or indirectly influence microbe-mediated bioactivation of the drug [4]. The hypoxic characteristics of the plateau environment have significant influences and constraints on the activities and behaviors of the living organisms, which can change the composition of intestinal microbes [5]. Furthermore, there is little research on the changes of pharmacokinetics mediated by intestinal flora under high-altitude hypoxia.…”

An in-depth analysis of the intestinal microbiome & metabolites of rats under high-altitude hypoxic-condition

“…For instance, high-altitude hypoxic conditions critically impact the individual's metabolite levels, vital enzymes, and metabolic pathways involved in in ammation and energy metabolism [3]. Besides, the intestinal micro ora also changes as a result of the major shift in the external atmospheric conditions at the same time [4].…”