Effect of zolpidem on human cytochrome P450 activity, and on transport mediated by P-glycoprotein

Biopharm Drug Dispos. 2002 Dec;23(9):361-7. doi: 10.1002/bdd.329.


The influence of high concentrations of zolpidem (100 microM, corresponding to approximately 200 times maximum therapeutic concentrations) on the activity of six human Cytochrome P450 (CYP) enzymes was evaluated in a model system using human liver microsomes. Zolpidem produced negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. Transport of rhodamine 123, presumed to be mediated mainly by the energy-dependent efflux transport protein P-glycoprotein, was studied in a cell culture system using a human intestinal cell line. High concentrations of zolpidem (100 microM), exceeding the usual therapeutic range by more than 100-fold, produced only modest impairment of rhodamine 123 transport. The findings indicate that zolpidem is very unlikely to cause clinical drug interactions attributable to impairment of CYP activity or P-gp mediated transport.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Biological Transport, Active / drug effects
  • Cells, Cultured
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism*
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism
  • Pyridines / pharmacology*
  • Rhodamine 123 / metabolism
  • Zolpidem


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cytochrome P-450 Enzyme Inhibitors
  • Isoenzymes
  • Pyridines
  • Rhodamine 123
  • Zolpidem
  • Cytochrome P-450 Enzyme System