Effect of Gut Microbiota on the Pharmacokinetics of Nifedipine in Spontaneously Hypertensive Rats

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.