A Review on Drug-Metabolizing Enzymes, Transporters, and Gut Microbiota on Pharmacokinetics in High-Altitude Environment.

Abstract

The most significant feature of the high-altitude environment is hypoxia, which affects the activity and expression of drug-metabolizing enzymes and transporters, leading to changes in pharmacokinetic parameters. Notably, gut microbiota is a hidden organ in the body. High-altitude hypoxia will change the composition and quantity of gut microbiota, affect drug metabolism, and change the bioavailability of drugs. This will provide a new perspective on changes in pharmacokinetics at high-altitude. Most studies have revealed that for drugs with low bioavailability and high clearance, the dosage may be increased accordingly. Conversely, the dosage may be reduced to achieve individualized medication. Therefore, this article reviews the changes and mechanisms of drug-metabolizing enzymes, transporters, and gut microbiota in a high-altitude environment and explains the impact of their changes on pharmacokinetics, aiming to provide theories and bases for the adjustment of drug dosage and the rational use of drugs in the clinic under high-altitude environment.