Gut microbiota modulates drug pharmacokinetics

Abstract

Gut microbiota, one of the determinants of pharmacokinetics, has long been underestimated. It is now generally accepted that the gut microbiota plays an important role in drug metabolism during enterohepatic circulation either before drug absorption or through various microbial enzymatic reactions in the gut. In addition, some drugs are metabolized by the intestinal microbiota to specific metabolites that cannot be formed in the liver. More importantly, metabolizing drugs through the gut microbiota prior to absorption can alter the systemic bioavailability of certain drugs. Therefore, understanding intestinal flora-mediated drug metabolism is critical to interpreting changes in drug pharmacokinetics. Here, we summarize the effects of gut microbiota on drug pharmacokinetics, and propose that the influence of intestinal flora on pharmacokinetics should be organically related to the therapeutic effects and side effects of drugs. More importantly, we could rationally perform the strategy of intestinal microflora-mediated metabolism to design drugs.

Keywords:

• Gut microbiota
• drug pharmacokinetics
• drug metabolism
• therapeutic effect
• toxicity

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This research was supported by the Lanzhou University (the Fundamental Research Funds for the Central Universities, lzujbky-2018-39), and National Natural Science Foundation of China (Nos. 81403004, 81673508, and 81401552), and Major project of “Twelfth Five-Year Plan” Military Logistics research (No. AWS14L005).