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Metabolic Fate of Felodipine in Man

In Search of New Dihydropyridine Metabolites

Summary

A new metabolic pathway for felodipine was confirmed by identification and quantification of new felodipine metabolites retaining the dihydropyridine structure. Following administration of a 10mg dose to 6 healthy subjects, felodipine was rapidly absorbed, reaching maximum plasma concentration (Cmax) [22.5 ng/ml] after 1.5 hours, and was then eliminated with a half-life of 3.1 hours. The pyridine metabolite had a similar plasma concentration-time course to that of the parent compound, with a Cmax of 30.1 ng/ml and an elimination half-life of 2.8 hours. In contrast, the dihydropyridine metabolite (5-carboxy derivative) reached a Cmax value (47.8 ng/ml) 1.9 hours after administration and was eliminated with a half-life of 8.1 hours. This plasma dihydropyridine metabolite was identified by GC-MS (GC-mass spectrometry) in comparison with the standard material. The dihydropyridine metabolite was not detectable in urine.

These results suggest that in contrast to current beliefs, felodipine is metabolised via ester hydrolysis with the dihydropyridine ring retained.

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Correspondence to Dr Yumi Ohtake.

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Ohtake, Y., Sakamoto, T., Nishioka, R. et al. Metabolic Fate of Felodipine in Man. Drug Invest 4, 528–534 (1992). https://doi.org/10.1007/BF03259219

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Keywords

  • Felodipine
  • Drug Invest
  • Dihydropyridine
  • Nisoldipine
  • Xenobiotic Metabolism