Artemisinin--a possible CYP2B6 probe substrate?

Biopharm Drug Dispos. 2009 Jul;30(5):265-75. doi: 10.1002/bdd.665.


Aim: To compare in vitro metabolism rates for artemisinin and the CYP2B6 substrates, bupropion, propofol and efavirenz in human liver microsomes.

Methods: Rate constants of artemisinin, bupropion, propofol and efavirenz metabolism by human liver microsomes from a panel of 12 donors, with different levels of CYP2B6 activity, were estimated in WinNonlin. Correlations between the metabolic rate constant for artemisinin and the other CYP2B6 substrates were examined.

Results: Artemisinin and propofol depletion data in human liver microsomes were described by first order kinetic models. For bupropion and efavirenz, metabolite formation data were incorporated in the model. Rate constants varied considerably for all substrates. There was a high degree of correlation of rate constants between substrates (r> or =0.87, p<0.001).

Conclusions: The rate of in vitro metabolism of artemisinin was correlated significantly to that of bupropion, propofol and efavirenz, suggesting artemisinin to be a potential alternative marker to assess CYP2B6 activity. Further studies characterizing the metabolic fate of artemisinin are needed in order to evaluate its utility as an in vitro and in vivo CYP2B6 probe substrate, since CYP2B6 might not be the only CYP isoform involved in the depletion of artemisinin.

MeSH terms

  • Alkynes
  • Anti-HIV Agents / metabolism
  • Antidepressive Agents, Second-Generation / metabolism
  • Antimalarials / metabolism*
  • Artemisinins / metabolism*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Benzoxazines / metabolism
  • Bupropion / metabolism
  • Chromatography, High Pressure Liquid
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6
  • Humans
  • Hypnotics and Sedatives / metabolism
  • In Vitro Techniques
  • Microsomes, Liver / metabolism
  • Oxidoreductases, N-Demethylating / metabolism*
  • Propofol / metabolism
  • Spectrophotometry, Ultraviolet


  • Alkynes
  • Anti-HIV Agents
  • Antidepressive Agents, Second-Generation
  • Antimalarials
  • Artemisinins
  • Benzoxazines
  • Cyclopropanes
  • Hypnotics and Sedatives
  • Bupropion
  • artemisinin
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Oxidoreductases, N-Demethylating
  • efavirenz
  • Propofol