'In vitro' interactions of monensin with hepatic xenobiotic metabolizing enzymes

Pharmacol Res. 1997 Sep;36(3):249-54. doi: 10.1006/phrs.1997.0226.


Monensin, a polyether ionophore antibiotic used worldwide for its anticoccidial and growth-promoting properties, is reported to act as anin vivo inducer or inhibitor of drug-metabolizing enzyme systems in various species according to dosage regimens and duration of exposure. When incubated at a concentration up to 0.25 mM with hepatic subfractions from either untreated- (UT) or phenobarbital- (PB) induced rats, monensin did not induce appreciable changes in cytochrome P450 content and functions as well as in NADPH cytochrome c reductase or glutathione S-transferase. On the other hand, monensin concentrations ranging from 0.05 to 0.25 mM proved to increase the initial rate of NADPH oxidation up to 63% in UT-microsomes, and the in vitro addition of the ionophore to microsomes resulted in the formation of a characteristic type I binding spectrum. The rate of monensin O-demethylation was 0.34+/-0. 01 and 0.99+/-0.07 nmol min-1 per mg of protein in UT- and PB-microsomes, respectively. In the latter, this reaction was consistently depressed when NADPH was omitted or replaced with NADH, or upon the addition of 1 mM metyrapone, a known P450 inhibitor. It is concluded that monensin does not behave as a direct in vitro inhibitor of drug metabolizing enzymes and appears to be a substrate of P450-dependent monooxygenases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coccidiostats / metabolism
  • Coccidiostats / pharmacology*
  • Cytochrome P-450 Enzyme System / drug effects*
  • Cytochrome P-450 Enzyme System / metabolism
  • Male
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology
  • Monensin / metabolism
  • Monensin / pharmacology*
  • Rats
  • Rats, Wistar


  • Coccidiostats
  • Cytochrome P-450 Enzyme System
  • Monensin