Drug-drug interactions: effect of quinidine on nifedipine binding to human cytochrome P450 3A4

Biochem Pharmacol. 1997 Feb 21;53(4):455-60. doi: 10.1016/s0006-2952(96)00836-2.


Quinidine is a known inhibitor of cytochrome P450-mediated nifedipine metabolism. The interactions of nifedipine and quinidine with human cytochrome P450 3A4, which metabolizes these drugs, were examined using the kinetics of CO binding to this P450 as a rapid kinetic probe of protein conformation and dynamics. This approach showed that nifedipine and quinidine bind to different P450 3A4 species, respectively termed species I and II, with distinct conformations. When both drugs were present simultaneously, nifedipine interacted with the quinidine-bound P450 species II, but not species I. These findings indicate that quinidine acts as an allosteric inhibitor by switching nifedipine binding from nifedipine-metabolizing species I to the nonmetabolizing species II.

MeSH terms

  • Anti-Arrhythmia Agents / pharmacology*
  • Calcium Channel Blockers / metabolism*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug Interactions
  • Humans
  • Mixed Function Oxygenases / metabolism*
  • Nifedipine / metabolism*
  • Quinidine / pharmacology*


  • Anti-Arrhythmia Agents
  • Calcium Channel Blockers
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Nifedipine
  • Quinidine