The System Profile of Renal Drug Transporters in Tubulointerstitial Fibrosis Model and Consequent Effect on Pharmacokinetics

Molecules

Baolin Huang¹  Menghua Liu¹  Zheng Cai¹  Birui Shi¹  Huiping Lin¹  Yan Zhang¹  Qiong Zhou²  Yujue Wang³ 

[1] Biopharmaceutics, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China;Integrated Traditional Chinese and Western Medicine Hospital of Southern Medical University, Southern Medical University, Guangzhou 510515, China;Laboratory Animal Management Center, Southern Medical University, Guangzhou 510515, China;

关键词: drug transporters;    pharmacokinetics;    OCT2;    MATE1;    P-gp;   

DOI  :  10.3390/molecules27030704

来源: DOAJ

【 摘 要 】

With the widespread clinical use of drug combinations, the incidence of drug–drug interactions (DDI) has significantly increased, accompanied by a variety of adverse reactions. Drug transporters play an important role in the development of DDI by affecting the elimination process of drugs in vivo, especially in the pathological state. Tubulointerstitial fibrosis (TIF) is an inevitable pathway in the progression of chronic kidney disease (CKD) to end-stage renal disease. Here, the dynamic expression changes of eleven drug transporters in TIF kidney have been systematically investigated. Among them, the mRNA expressions of Oat1, Oat2, Oct1, Oct2, Oatp4C1 and Mate1 were down-regulated, while Oat3, Mrp2, Mrp4, Mdr1-α, Bcrp were up-regulated. Pearson correlation analysis was used to analyze the correlation between transporters and Creatinine (Cr), OCT2 and MATE1 showed a strong negative correlation with Cr. In contrast, Mdr1-α exhibited a strong positive correlation with Cr. In addition, the pharmacokinetics of cimetidine, ganciclovir, and digoxin, which were the classical substrates for OCT2, MATE1 and P-glycoprotein (P-gp), respectively, have been studied. These results reveal that changes in serum creatinine can indicate changes in drug transporters in the kidney, and thus affect the pharmacokinetics of its substrates, providing useful information for clinical use.

【 授权许可】

Unknown