In vitro evaluation of the metabolic enzymes and drug interaction potential of triapine

Anand Joshi, Brian F. Kiesel, Nupur Chaphekar, Reyna Jones, Jianxia Guo, Charles A. Kunos, Sarah Taylor, Edward Chu, Raman Venkataramanan, Jan H. Beumer

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Purpose: To investigate the metabolic pathways of triapine in primary cultures of human hepatocytes and human hepatic subcellular fractions; to investigate interactions of triapine with tenofovir and emtricitabine; and to evaluate triapine as a perpetrator of drug interactions. The results will better inform future clinical studies of triapine, a radiation sensitizer currently being studied in a phase III study. Methods: Triapine was incubated with human hepatocytes and subcellular fractions in the presence of a number of inhibitors of drug metabolizing enzymes. Triapine depletion was monitored by LC–MS/MS. Tenofovir and emtricitabine were co-incubated with triapine in primary cultures of human hepatocytes. Triapine was incubated with a CYP probe cocktail and human liver microsomes, followed by LC–MS/MS monitoring of CYP specific metabolite formation. Results: Triapine was not metabolized by FMO, AO/XO, MAO-A/B, or NAT-1/2, but was metabolized by CYP450s. CYP1A2 accounted for most of the depletion of triapine. Tenofovir and emtricitabine did not alter triapine depletion. Triapine reduced CYP1A2 activity and increased CYP2C19 activity. Conclusion: CYP1A2 metabolism is the major metabolic pathway for triapine. Triapine may be evaluated in cancer patients in the setting of HIV with emtricitabine or tenofovir treatment. Confirmatory clinical trials may further define the in vivo triapine metabolic fate and quantify any drug–drug interactions.

Original languageEnglish (US)
Pages (from-to)633-640
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Issue number5
StatePublished - Nov 1 2020
Externally publishedYes


  • CYP450
  • Drug–drug interaction
  • Metabolic pathway
  • Metabolism
  • Triapine

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)


Dive into the research topics of 'In vitro evaluation of the metabolic enzymes and drug interaction potential of triapine'. Together they form a unique fingerprint.

Cite this