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Effects of Compound Probiotics on Pharmacokinetics of Cytochrome 450 Probe Drugs in Rats. | LitMetric
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Effects of Compound Probiotics on Pharmacokinetics of Cytochrome 450 Probe Drugs in Rats.

Yanjuan Zhang Zhi Chen Yayi Xiao Tianyuan Wu Haijun Yang Yujie Liu Rong Zhou Yalan Xiong Yanling Xiong Xuechun Yang Jian Zhou Honghao Zhou Wei Zhang Yan Shu Xiong Li Fugang Guo Jianhui Yin Shang Liao Qing Li Peng Zhu

Drug Metab Dispos

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China (Y.Z., Y.X., T.W., H.Y., Y.L., R.Z., Yal.X., Yan.X., X.Y., J.Z., H.Z., W.Z., Q.L., P.Z.); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China (Y.Z., Y.X., T.W., H.Y., Y.L., R.Z., Yal.X., Yan.X., X.Y., J.Z., H.Z., W.Z., Q.L., P.Z.); Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China (Y.Z., Y.X., T.W., H.Y., Y.L., R.Z., Yal.X., Yan.X., X.Y., J.Z., H.Z., W.Z., Q.L., P.Z.); National Clinical Research Center for Geriatric Disorders, Changsha, China (Y.Z., Y.X., T.W., H.Y., Y.L., R.Z., Yal.X., Yan.X., X.Y., J.Z., H.Z., W.Z., Q.L., P.Z.); Department of Hypertension, Xingsha Hospital, Changsha, China (Z.C., F.G., J.Y., S.L.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, Maryland (Y.S.); and Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China (X.L.)

Published: October 2024

AI Article Synopsis

  • The study investigates how the compound probiotic VSL#3 affects the metabolism of various cytochrome P450 enzyme probe drugs in male Wistar rats.
  • Results show that VSL#3 alters the gut microbiota, leading to significant increases in the bioavailability of certain drugs, like omeprazole, while decreasing the bioavailability of others like tolbutamide and chlorpropamide.
  • Additionally, the administration of VSL#3 impacted gene expression related to drug metabolism and intestinal structure, suggesting that probiotics can influence how drugs are processed in the body.

Article Abstract

Compound probiotics have been widely used and commonly coadministered with other drugs for treating various chronic illnesses, yet their effects on drug pharmacokinetics remain underexplored. This study elucidated the impact of VSL#3 on the metabolism of probe drugs for cytochrome P450 enzymes (P450s), specifically omeprazole, tolbutamide, midazolam, metoprolol, phenacetin, and chlorzoxazone. Male Wistar rats were administered drinking water containing VSL#3 or not for 14 days and then intragastrically administered a P450 probe cocktail; this was done to investigate the host P450's metabolic phenotype. Stool, liver/jejunum, and serum samples were collected for 16S ribosomal RNA sequencing, RNA sequencing, and bile acid profiling. The results indicated significant differences in both and diversity of intestinal microbial composition between the probiotic and vehicle groups in rats. In the probiotic group, the bioavailability of omeprazole increased by 269.9%, whereas those of tolbutamide and chlorpropamide decreased by 28.1% and 27.4%, respectively. The liver and jejunum exhibited 1417 and 4004 differentially expressed genes, respectively, between the two groups. In the probiotic group, most of P450 genes were upregulated in the liver but downregulated in the jejunum. The expression of genes encoding metabolic enzymes and drug transporters also changed. The serum-conjugated bile acids in the probiotic group were significantly reduced. Shorter duodenal villi and longer ileal villi were found in the probiotic group. In summary, VSL#3 administration altered the gut microbiota, host drug-processing gene expression, and intestinal structure in rats, which could be reasons for pharmacokinetic changes. SIGNIFICANCE STATEMENT: This study focused on the effects of the probiotic VSL#3 on the pharmacokinetic profile of cytochrome P450 probe drugs and the expression of host drug metabolism genes. Compared with previous studies, the present study provides a comprehensive explanation for the host drug metabolism profile modified by probiotics, combined here with the bile acid profile and histopathological analysis.

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 Source
http://dx.doi.org/10.1124/dmd.124.001837DOI Listing

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