Evidence of an interaction between nifedipine and nafcillin in humans

Lang, C.C.; Jamal, S.K.; Mohamed, Z.; Mustafa, M.R.; Mustafa, A.M.; Lee, T.C. (2003) Evidence of an interaction between nifedipine and nafcillin in humans. British Journal of Clinical Pharmacology, 55 (6). pp. 588-590. ISSN 1365-2125

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    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�α) in nafcillin-pretreated subjects (80.9 ± 32.9 µg l�1 h�1) was significantly decreased compared with subjects who received only nifedipine (216.4 ± 93.2 µg 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�1vs 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.

    Item Type: Article
    1. Lang, C.C.
    2. Jamal, S.K.
    3. Mohamed, Z.
    4. Mustafa, M.R.(Department of Pharmacology, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, MALAYSIA)
    5. Mustafa, A.M.
    6. Lee, T.C.
    Journal or Publication Title: British Journal of Clinical Pharmacology
    Additional Information: suggested citation : Lang CC, Jamal SK, Mohamed Z, Mustafa MR, Mustafa AM, Lee TC. Evidence of an interaction between nifedipine and nafcillin in humans. British journal of clinical pharmacology. 2003;55(6):588-90.
    Uncontrolled Keywords: Cytochrome P450; Drug interaction; Nafcillin; Nifedipine
    Subjects: R Medicine
    Divisions: Faculty of Medicine > School of Biological Sciences
    Depositing User: Ms Haslinda Lahuddin
    Date Deposited: 08 May 2012 11:23
    Last Modified: 20 Oct 2014 16:02
    URI: http://eprints.um.edu.my/id/eprint/3033

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