Evidence of an interaction between nifedipine and nafcillin in humans.

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.