In vitro and in silico identification and characterization of thiabendazole as a mechanism-based inhibitor of CYP1A2 and simulation of possible pharmacokinetic drug-drug interactions.

@article{Thelingwani2009InVA,
  title={In vitro and in silico identification and characterization of thiabendazole as a mechanism-based inhibitor of CYP1A2 and simulation of possible pharmacokinetic drug-drug interactions.},
  author={Roslyn S. Thelingwani and Simbarashe Peter Zvada and Hugues Dolgos and Anna-Lena B. Ungell and Collen M. Masimirembwa},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2009},
  volume={37 6},
  pages={1286-94}
}
Thiabendazole (TBZ) and its major metabolite 5-hydroxythiabendazole (5OH-TBZ) were screened for potential time-dependent inhibition (TDI) against CYP1A2. Screen assays were carried out in the absence and presence of NADPH. TDI was observed with both compounds, with k(inact) and K(I) values of 0.08 and 0.02 min(-1) and 1.4 and 63.3 microM for TBZ and 5OH-TBZ, respectively. Enzyme inactivation was time-, concentration-, and NADPH-dependent. Inactivation by TBZ was irreversible by dialysis and… CONTINUE READING