Emerging evidence of inter-organ interaction on drug transporters under liver injury

Dysfunction of drug transporters is an important cause of abnormal effects and implications for drug therapy in liver injury patients. Clinical and experimental data show that liver injury is associated with inter-organ interaction in brain, eye, liver, intestine and kidney. Recent advancements in basic and clinical research have demonstrated physiologic and molecular mechanisms of transporter alterations in liver injury, including bilirubin, reactive oxygen species, ammonia, bile acid, inflammatory factors and so on. It is important to note that the impact of these transporter changes on pharmacokinetics of therapeutic medicine in liver injury patients remains largely unexplored. Consequently, further research is necessary to better understand these effects and their implications for drug therapy in liver disease patients. The well-characterized changes of transporters in distant organ across different types of liver diseases suggest that dosage adjustments may be indispensable when treating patients with liver dysfunction using drugs that are substrates for these transporters, including traditional Chinese and Western medicine. This ensures drug concentrations remain within therapeutic window and adverse drug reactions are minimized. Equal importance is that when using inducers or inhibitors of drug transporters in clinical practice, it is crucial to consider long-term effects on transporters and its potential for drug therapy. Care should be taken to avoid impairing the clearance of toxic metabolites and proteins when inhibiting these transporters. Similarly, caution is required when using inducers or inducer-type therapeutic drugs to avoid aggravating drug resistance. This paper overviews recent clinical and experimental findings on the inter-organ interaction on drug transporters under liver injury status and their clinical significances.