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Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

Objective

To evaluate felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions (PK-DDIs) involving cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp).

Methods

Felodipine extended-release 10 mg was administered daily to six healthy subjects for 7 days (days 1–7). Subjects were administered a modified Inje cocktail comprising the selective probe substrates caffeine 100 mg (CYP1A2), losartan 25 mg (CYP2C9), omeprazole 20 mg (CYP2C19), dextromethorphan 30 mg (CYP2D6), midazolam 2 mg (CYP3A) and digoxin 250 μg (P-gp) on day 0 (prior to felodipine exposure) and day 7 (after felodipine exposure). Plasma samples were collected over 24 h and drug concentrations measured by UPLC-MS/MS.

Results

The geometric means of the area under the plasma concentration–time curve ratios (probe AUC after felodipine exposure/probe AUC prior to felodipine exposure) and 95 % confidence intervals for each probe were: caffeine 0.91 (0.64–1.30), losartan 1.05 (0.95–1.15), omeprazole 1.17 (0.78–1.76), dextromethorphan 1.46 (1.00–2.12), midazolam 1.23 (0.99–1.52) and digoxin 1.01 (0.89–1.15).

Conclusion

Felodipine may be a weak in vivo inhibitor of CYP3A and CYP2D6 but is unlikely to act as a significant perpetrator of PK-DDIs.

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Acknowledgments

We thank Prof. Martin Kennedy and Ms. Allison Miller at the Carney Centre for Pharmacogenomics (University of Otago, Christchurch, New Zealand) for CYP2D6 genotyping. We also thank Dr. Helen Healy for clinical support during the study visits and Dr. Ganessan Kichenadasse for useful feedback on the study design.

Conflict of interest

None declared.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology, Flinders University and Flinders Medical Centre, Sturt Rd, Bedford Park, Adelaide, SA, 5042, Australia

    Ben D. Snyder, Andrew Rowland, Thomas M. Polasek & John O. Miners

  2. Department of Medicine, University of Otago, Christchurch, New Zealand

    Matthew P. Doogue

Authors
  1. Ben D. Snyder
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  2. Andrew Rowland
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  3. Thomas M. Polasek
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  4. John O. Miners
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Corresponding author

Correspondence to Thomas M. Polasek.

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Snyder, B.D., Rowland, A., Polasek, T.M. et al. Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions. Eur J Clin Pharmacol 70, 1115–1122 (2014). https://doi.org/10.1007/s00228-014-1716-8

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  • DOI: https://doi.org/10.1007/s00228-014-1716-8

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