In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations in human liver microsomes: a comparison with SKF-525A

Drug Metab Pharmacokinet. 2005 Oct;20(5):351-7. doi: 10.2133/dmpk.20.351.


1-Aminobenzotriazole (ABT) is extensively used as a non-specific cytochrome P450 (CYP) inhibitor. In this study, the inhibitory effect of ABT on CYP-dependent drug oxidations was investigated in human liver microsomes (HLM) and compared with that of SKF-525A, another non-specific inhibitor. The following probe activities for human CYP isoforms were determined using pooled HLM: phenacetin O-deethylation (CYP1A2); diclofenac 4'-hydroxylation (CYP2C9); S-mephenytoin 4'-hydroxylation, (CYP2C19); bufuralol 1'-hydroxylation (CYP2D6); chlorzoxazone 6-hydroxylation (CYP2E1); midazolam 1'-hydroxylation, nifedipine oxidation, and testosterone 6beta-hydroxylation (CYP3A). ABT had the strongest inhibitory effect on the CYP3A-dependent drug oxidations and the weakest effect on the diclofenac 4'-hydroxylation. SKF-525A potently inhibited the bufuralol 1'-hydroxylation, but weakly inhibited chlorzoxazone 6-hydroxylation. The inhibitory effects of ABT and SKF-525A were increased by preincubation in some probe reactions, and this preincubation effect was greater in ABT than in SKF-525A. The remarkable IC50 shift (> 10 times) by preincubation with ABT was observed on the phenacetin O-deethylation, chlorzoxazone 6-hydroxylation, and midazolam 1'-hydroxylation. In conclusion, ABT and SKF-525A had a wide range of IC50 values in inhibiting the drug oxidations by HLM with and without preincubation.

Publication types

  • Comparative Study

MeSH terms

  • Cytochrome P-450 Enzyme Inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Isoenzymes / antagonists & inhibitors
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / metabolism
  • Oxidation-Reduction / drug effects
  • Proadifen / pharmacology*
  • Substrate Specificity
  • Triazoles / pharmacology*


  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Isoenzymes
  • Triazoles
  • 1-aminobenzotriazole
  • Proadifen