Pharmacokinetics of the enantiomers of felodipine in the dog after oral and intravenous administration of a pseudoracemic mixture

Abstract

1. A pseudoracemic mixture of deuterated (S)-felodipine and unlabelled (R)-felodipine was administered as single i.v. or oral doses to four dogs. Plasma concentrations of the enantiomers and their corresponding pyridine metabolites were determined by g.l.c.-mass spectrometry.

2. No isotope effects were observed after oral administration of equimolar amounts of deuterated and unlabelled (S)-felodipine.

3. The pharmacokinetic parameters of the enantiomers were similar after i.v. administration, indicating that the disposition of felodipine was not stereoselective.

4. After oral administration the bioavailability of (R)-felodipine was slightly higher than that of (S)-felodipine in two of the dogs, presumably due to a lower first-pass extraction of the (R)-enantiomer, while no difference was observed in the other two dogs.

5. No substantial differences in C_max or AUC were observed between the deuterated and unlabelled pyridine metabolites, indicating that the oxidative clearances of the felodipine enantiomers were similar. Magnar Ervik and Britt Yhlen are gratefully acknowledged for performing the g.l.c.-mass spectrometry analysis of the plasma samples.