title: Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions.
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).
  
  
  CONCLUSIONS
  Felodipine may be a weak in vivo inhibitor of CYP3A and CYP2D6 but is unlikely to act as a significant perpetrator of PK-DDIs.
authors.affiliation: Department of Clinical Pharmacology, Flinders University and Flinders Medical Centre, Sturt Rd, Bedford Park, Adelaide, SA, 5042, Australia.
authors.forename: Ben D
authors.initials: BD
authors.lastname: Snyder
authors.forename: Andrew
authors.initials: A
authors.lastname: Rowland
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Polasek
authors.forename: John O
authors.initials: JO
authors.lastname: Miners
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Doogue
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003915:Dextromethorphan / Q000097:blood / Q000493:pharmacokinetics; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics; D004347:Drug Interactions; D015736:Felodipine / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D019808:Losartan / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics; D009853:Omeprazole / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D065607:Cytochrome P-450 Enzyme Inhibitors; D002110:Caffeine; D003915:Dextromethorphan; D004077:Digoxin; D003577:Cytochrome P-450 Enzyme System; D019808:Losartan; D009853:Omeprazole; D015736:Felodipine; D008874:Midazolam