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Interactions between cyazofamid and human drug transporters
Author(s) -
Song ImSook,
Jeong HyeonUk,
Choi MinKoo,
Kwon Mihwa,
Shin Yongho,
Kim Jeong Han,
Lee HyeSuk
Publication year - 2020
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22459
Subject(s) - transporter , pharmacology , chemistry , drug , atp binding cassette transporter , organic anion transporting polypeptide , p glycoprotein , multiple drug resistance , biochemistry , medicine , gene , antibiotics
We aimed to investigate the intestinal permeability and interaction of cyazofamid with clinically important transporters. The intestinal permeability of cyazofamid was low (0.21 ± 0.02 cm/s), and it is a substrate for P‐glycoprotein (P‐gp) with a K m value of 83.1 μM, indicated that P‐gp in the intestinal lumen could serve as a protective barrier to this fungicide. Cyazofamid was not a substrate for clinically important transporters. However, cyazofamid inhibited organic cation transporter 3 (OCT3) and OAT1, with IC 50 values of 1.54 and 17.3 μM, respectively, but could not result in OAT3‐ and OAT1‐mediated cyazofamid‐drug interactions because of its low plasma concentration. Cyazofamid poorly interacted with OCT1, OCT2, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, P‐gp, breast cancer resistance‐related protein, and multidrug resistance‐related protein 2. In conclusion, the interactions of cyazofamid with human drug transporters have been evaluated as part of the safety assessment. Given its low intestinal permeability and poor interaction with human drug transporters, cyazofamid might not cause serious toxicity or adverse events.