title: Investigation of bioequivalence of a new fixed-dose combination of nifedipine and candesartan with the corresponding loose combination as well as the drug-drug interaction potential between both drugs under fasting conditions.
abstract: OBJECTIVE
  To determine the bioequivalence of a nifedipine and candesartan fixed-dose combination (FDC) with the corresponding loose combination, and to investigate the pharmacokinetic drug-drug interaction potential between both drugs.
  
  
  METHODS
  49 healthy, white, male subjects received: 60 mg nifedipine and 32 mg candesartan FDC, the loose combination of 60 mg nifedipine GITS and 32 mg candesartan, 60 mg nifedipine GITS alone, or 32 mg candesartan alone in a randomized, non-blinded, 4-period, 4-way crossover design with each dosing following overnight fasting. Treatment periods were separated by washout periods of ≥ 5 days. Plasma samples were collected for 48 hours after dosing and assayed using a validated LC-MS/MS method.
  
  
  RESULTS
  Bioequivalence between the FDC and the loose combination as well as the impact of combined treatment with both drugs on candesartan pharmacokinetics was evaluated in 47 subjects, while the corresponding impact of treatment with both drugs on nifedipine pharmacokinetics was assessed in 46 patients. For AUC(0-tlast) and Cmax the 90% confidence intervals (CIs) for the ratios of the FDC vs. the corresponding loose combination were within the acceptance range for bioequivalence of 80 - 125%. When comparing AUC(0-tlast) and Cmax of nifedipine and candesartan after dosing with the loose combination vs. each drug alone, the 90% CIs remained within the range of 80 - 125% indicating the absence of a clinically relevant pharmacokinetic drug-drug interaction. Nifedipine and candesartan as well as the combinations were well tolerated.
  
  
  CONCLUSIONS
  The FDC containing 60 mg nifedipine and 32 mg candesartan was bioequivalent to the corresponding loose combination following single oral doses under fasting conditions. No clinically relevant pharmacokinetic drug-drug interaction between nifedipine and candesartan was observed.
authors.forename: Erich
authors.initials: E
authors.lastname: Brendel
authors.forename: Boris
authors.initials: B
authors.lastname: Weimann
authors.forename: Hartmut
authors.initials: H
authors.lastname: Dietrich
authors.forename: Christoph
authors.initials: C
authors.lastname: Froede
authors.forename: Dirk
authors.initials: D
authors.lastname: Thomas
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013777:Tetrazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D013777:Tetrazoles; D009543:Nifedipine; C081643:candesartan