[OATP1B1 in drug-drug interactions between traditional Chinese medicine Danshensu and rosuvastatin].

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  • Additional Information
    • Source:
      Publisher: Zhongguo yao xue hui Country of Publication: China NLM ID: 21710340R Publication Model: Print Cited Medium: Print ISSN: 0513-4870 (Print) Linking ISSN: 05134870 NLM ISO Abbreviation: Yao Xue Xue Bao Subsets: MEDLINE
    • Publication Information:
      Original Publication: Beijing : Zhongguo yao xue hui
    • Subject Terms:
      Drugs, Chinese Herbal/*pharmacology ; Hepatocytes/*drug effects ; Lactates/*pharmacology ; Organic Anion Transporters/*metabolism ; Rosuvastatin Calcium/*pharmacology; Animals ; Drug Interactions ; HEK293 Cells ; Hepatocytes/metabolism ; Humans ; Liver-Specific Organic Anion Transporter 1 ; Rats
    • Abstract:
      The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.
    • Accession Number:
      0 (Drugs, Chinese Herbal)
      0 (Lactates)
      0 (Liver-Specific Organic Anion Transporter 1)
      0 (Organic Anion Transporters)
      0 (SLCO1B1 protein, human)
      4GF33A5PAJ (3,4-dihydroxyphenyllactic acid)
      83MVU38M7Q (Rosuvastatin Calcium)
    • Publication Date:
      Date Created: 20160714 Date Completed: 20160722 Latest Revision: 20181202
    • Publication Date:
      20240829
    • Accession Number:
      27405165