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Evidence of an interaction between nifedipine and nafcillin in humans.

Author(s): Lang CC, Jamal SK, Mohamed Z, Mustafa MR, Mustafa AM, Lee TC

Affiliation(s): Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. chimlang@hotmail.com

Publication date & source: 2003-06, Br J Clin Pharmacol., 55(6):588-90.

Publication type: Clinical Trial; Randomized Controlled Trial

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.

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