Evidence of an interaction between nifedipine and nafcillin in humans

Br J Clin Pharmacol. 2003 Jun;55(6):588-90. doi: 10.1046/j.1365-2125.2003.01789.x.


Aims: Nafcillin (Wyeth Laboratories, Philadelphia, PA, USA) has been reported to induce the metabolism of cyclosporin and warfarin, which are known substrates of cytochrome P-450 (CYP). However, there has not been any report to date on its possible interaction with nifedipine, an index substrate of the enzyme, CYP3A4.

Methods: Nine healthy normotensive subjects participated in this randomized placebo-controlled two-way crossover study examining the effects of 5 days' pretreatment of nafcillin 500 mg or placebo four times daily on the pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine concentrations were measured by gas chromatography-mass spectro.

Results: The area under the plasma nifedipine concentration-time curve (AUC0-alpha) in nafcillin-pretreated subjects (80.9 +/- 32.9 micro g l-1 h-1) was significantly decreased compared with subjects who received only nifedipine (216.4 +/- 93.2 micro g l-1 h-1) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h-1 vs 56.5 +/- 32.0 l h-1) (P < 0.002).

Conclusions: The results show that nafcillin pretreatment markedly increased the clearance of nifedipine and suggest that nafcillin is a potent inducer of CYP enzyme.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Cross-Over Studies
  • Drug Interactions
  • Humans
  • Male
  • Nafcillin / blood
  • Nafcillin / pharmacokinetics*
  • Nifedipine / blood
  • Nifedipine / pharmacokinetics*
  • Penicillins / blood
  • Penicillins / pharmacokinetics*


  • Penicillins
  • Nafcillin
  • Nifedipine