Is quinine a suitable probe to assess the hepatic drug-metabolizing enzyme CYP3A4?

Br J Clin Pharmacol. 2002 Dec;54(6):643-51. doi: 10.1046/j.1365-2125.2002.01687.x.


Aims: To evaluate the antimalarial agent quinine as a potential in vivo probe for hepatic cytochrome P450 (CYP) 3A4 activity.

Methods: Ten healthy adult volunteers received, by randomized crossover design, either a single oral dose of quinine sulphate (600 mg) alone, or quinine sulphate (600 mg) plus the CYP3A4 inhibitor troleandomycin (TAO; 500 mg every 8 h). Plasma and urine samples were collected before quinine administration, and up to 48 h thereafter, then analysed by h.p.l.c. for both quinine and its CYP3A4-generated metabolite, 3-hydroxyquinine. During both phases, the erythromycin breath test (ERMBT) was administered at specific times to assess hepatic CYP3A4 activity.

Results: Compared with control, TAO treatment significantly decreased the mean time-averaged ERMBT result by 77% (95% CI, 68, 85%), the mean apparent oral clearance of quinine (CL/F ) by 45% (95% CI, 39, 52%), and the mean apparent formation clearance of 3-hydroxyquinine (CL3-OH) by 81% (95% CI, 76, 87%). There was no correlation between the TAO-mediated percent decrease in the time-averaged ERMBT result and the percent decrease in CL/F or in CL3-OH. When TAO and control treatments were analysed separately, there were no significant correlations between the time-averaged ERMBT result and CL/F, CL3-OH, or single plasma quinine concentration at 12, 24, and 48 h.

Conclusions: Quinine may be a useful probe to detect inhibition of liver CYP3A4 activity within an individual. Further studies are needed to determine whether it can provide a quantitative measure of CYP3A4 activity suitable for intersubject comparison.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antimalarials / administration & dosage
  • Antimalarials / blood
  • Antimalarials / pharmacokinetics*
  • Area Under Curve
  • Breath Tests / methods
  • Cross-Over Studies
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dose-Response Relationship, Drug
  • Erythromycin
  • Female
  • Humans
  • Liver / metabolism*
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Molecular Probes
  • Ovarian Neoplasms / metabolism
  • Quinidine / analogs & derivatives*
  • Quinidine / blood
  • Quinine / administration & dosage
  • Quinine / blood
  • Quinine / pharmacokinetics*
  • Troleandomycin / administration & dosage


  • Antimalarials
  • Molecular Probes
  • 3-hydroxyquinidine
  • Erythromycin
  • Cytochrome P-450 Enzyme System
  • Quinine
  • Troleandomycin
  • Quinidine