Chloroquine modulation of specific metabolizing enzymes activities: investigation with selective five drug cocktail

Br J Clin Pharmacol. 1998 Sep;46(3):215-9. doi: 10.1046/j.1365-2125.1998.00765.x.


Aims: The aim of this study was to investigate whether chloroquine can inhibit drug metabolism in humans, if such inhibition is general or selective for certain enzymes and evaluate the potential for and clinical significance of any drug-drug interactions when chloroquine is co-administered with other drugs.

Methods: The study was conducted in fourteen normal non-smoking healthy male volunteers using a cocktail of five drugs consisting of caffeine, mephenytoin, debrisoquine, chlorzoxazone and dapsone to assess activities of cytochromes P450 (CYP) 1A2, 2C19, 2D6, 2E1 and 3A4 respectively. Dapsone was also used to assess N-acetyltransferase activity. The activities were assessed at baseline, after one and seven daily doses (250 mg daily) of chloroquine and 7 and 14 days after stopping chloroquine dosing.

Results: Chloroquine caused a progressive and significant decrease in CYP2D6 activity as measured by debrisoquine metabolism from first to seventh dose and the activity returned to baseline gradually over 14 days after stopping administration. There was no effect on the metabolism of any of the other probe drugs.

Conclusions: Chloroquine has been shown to be capable of inhibiting the activity of CYP2D6 in vivo in humans. This effect is selective as activities of other enzymes investigated were not affected. The effect was modest but suggests a potential for drug-drug interactions when co-administered with other drugs that are substrates for this enzyme. The clinical significance of such an interaction will depend on the therapeutic index of any drug involved.

Publication types

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

MeSH terms

  • Adult
  • Analysis of Variance
  • Antimalarials / administration & dosage
  • Antimalarials / pharmacology*
  • Caffeine / administration & dosage
  • Chloroquine / administration & dosage
  • Chloroquine / pharmacology*
  • Chlorzoxazone / administration & dosage
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / metabolism
  • Dapsone / administration & dosage
  • Debrisoquin / administration & dosage
  • Debrisoquin / metabolism
  • Drug Administration Schedule
  • Drug Interactions
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / metabolism
  • Male
  • Phenotype


  • Antimalarials
  • Cytochrome P-450 Enzyme Inhibitors
  • Isoenzymes
  • Caffeine
  • Chloroquine
  • Dapsone
  • Cytochrome P-450 Enzyme System
  • Chlorzoxazone
  • Debrisoquin