Effect of Gut Microbiota on the Pharmacokinetics of Nifedipine in Spontaneously Hypertensive Rats
نویسندگان
چکیده
The pharmacokinetic variability of nifedipine widely observed in the clinic cannot be fully explained by pharmacogenomics. As a new factor affecting drug metabolism, how gut microbiota affects pharmacokinetics needs to explored. Spontaneously hypertensive rats (SHRs) have been commonly used hypertension-related research and served as experimental groups; Wistar were control groups. In this study, bioavailability decreased 18.62% (p < 0.05) SHRs compared with rats. Changes associated difference pharmacokinetics. relative abundance Bacteroides dorei was negatively correlated AUC0–t (r = −0.881, p 0.004) Cmax −0.714, 0.047). Analysis serum bile acid (BA) profiles indicated that glycoursodeoxycholic (GUDCA) glycochenodeoxycholic (GCDCA) significantly increased SHRs. Compared rats, expressions CYP3A1 PXR upregulated enzyme activity Spearman’s rank correlation revealed stercoris GUDCA −0.7126, 0.0264) GCDCA −0.6878, 0.0339). Moreover, −0.556, 0.025). primary rat hepatocytes, could induce target genes Mdr1a. Furthermore, antibiotic treatments verified impact on nifedipine. Generally, through microbial biotransformation or regulating CYP3A1.
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ژورنال
عنوان ژورنال: Pharmaceutics
سال: 2023
ISSN: ['1999-4923']
DOI: https://doi.org/10.3390/pharmaceutics15082085