Emerging evidence of inter-organ interaction on drug transporters under liver injury.
10.1016/S1875-5364(25)60888-0
- Author:
Ling JIANG
1
;
Ying DENG
1
;
Ruijing MU
1
;
Wenke FENG
1
;
Xiaonan LIU
2
;
Li LIU
3
Author Information
1. Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
2. Animal Experimental Center, China Pharmaceutical University, Nanjing 211198, China.
3. Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: liulee@cpu.edu.cn.
- Publication Type:Review
- Keywords:
Drug transporters;
Dysfunction;
Inter-organ interaction;
Liver injury;
Pharmacokinetics
- MeSH:
Humans;
Liver/drug effects*;
Animals;
Chemical and Drug Induced Liver Injury/metabolism*;
Membrane Transport Proteins/metabolism*;
Biological Transport;
Liver Diseases/drug therapy*;
Pharmaceutical Preparations/metabolism*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(6):687-699
- CountryChina
- Language:English
-
Abstract:
Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
