title: Stereoselective pharmacokinetics of oral felodipine and nitrendipine in healthy subjects: correlation with nifedipine pharmacokinetics.
abstract: The pharmacokinetics of racemic (rac) felodipine, rac-nitrendipine and nifedipine (all given as an oral dose of 20 mg in solution) have been investigated in a randomised cross-over study in 12 healthy male subjects using stereoselective assays. Both felodipine and nitrendipine exhibited stereoselective pharmacokinetics. On average, the AUCs of the active (S)-enantiomers of felodipine and nitrendipine were 139% and 104% higher than those of their optical antipodes, but the elimination half-lives of the enantiomers of each racemate were not different. The AUCs of nifedipine, rac-felodipine, rac-nitrendipine and of their enantiomers were highly correlated (all r > 0.83), suggesting closely related rate limiting steps in the in vivo first-pass metabolism of these high-clearance drugs. Stereoselectivity was only a minor contributor to inter-individual variability in the oral pharmacokinetics of these compounds in healthy subjects.
authors.affiliation: Center for Bio-Pharmaceutical Sciences, University of Leiden, The Netherlands.
authors.forename: P A
authors.initials: PA
authors.lastname: Soons
authors.forename: T M
authors.initials: TM
authors.lastname: Mulders
authors.forename: E
authors.initials: E
authors.lastname: Uchida
authors.forename: H C
authors.initials: HC
authors.lastname: Schoemaker
authors.forename: A F
authors.initials: AF
authors.lastname: Cohen
authors.forename: D D
authors.initials: DD
authors.lastname: Breimer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D004311:Double-Blind Method; D015736:Felodipine / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000097:blood / Q000493:pharmacokinetics*; D009568:Nitrendipine / Q000097:blood / Q000493:pharmacokinetics*; D011725:Pyridines / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D001798:Blood Proteins; D011725:Pyridines; D009568:Nitrendipine; D009543:Nifedipine; D015736:Felodipine