title: Bioequivalence study of an extemporaneously prepared oral solution of amlodipine suitable for use in pediatric patients compared to commercial tablets.
abstract: OBJECTIVE
  Amlodipine, a long-acting dihydropyridine calcium channel blocker, is frequently prescribed to pediatric patients. To date, no suitable pediatric formulation has been available. In this study, an amlodipine oral solution was developed and tested for bioequivalence to tablets in healthy adult volunteers.
  
  
  METHODS
  This study was designed as an open-label, single-dose, twosequence, two-period, crossover trial to assess the bioequivalence of a newly developed amlodipine besylate oral solution 0.5 mg/mL compared to Norvasc® 5 mg tablets. 13 adult subjects (mean [standard deviation] age of 23.2 [3.6] years, weight 71.5 [7.7] kg) were included and blood samples were collected for 72 hours. Amlodipine plasma levels were determined using a validated UPLC-MS/MS assay. Non-compartmental pharmacokinetic parameters were compared between the formulations according to European Medicines Agency (EMA) bioequivalence guidelines.
  
  
  RESULTS
  The 90% confidence intervals of the test/reference ratios of the geometric means for the primary pharmacokinetic parameters AUC(0-72) (88.24 - 104.37%) and C(max) (99.00 - 121.40%) were within the acceptance range of 80.00 - 125.00% for bioequivalence. Mean (SD) AUC(0-72) was 102.7 (26.8) (26.8) μg × h/L for the solution and 108.2 (30.6) μg × h/L for the tablet. Mean (SD) Cmax of the solution was 3.11(1.06) μg/L with a median (IQR) t(max) of 4.0 (2.6 - 7.5) hours. Mean (SD) C(max) of the tablet was 2.91 (0.84) μg/L with a median (IQR) tmax of 6.0 (4.0 - 14.0) hours. Intrasubject coefficients of variation were 10.2% (AUC(0-72)) and 12.4% (C(max)).
  
  
  CONCLUSIONS
  The formulations are bioequivalent according to EMA guidelines. This warrants further study of our novel amlodipine oral solution in pediatric patients.
authors.forename: Anna C
authors.initials: AC
authors.lastname: van der Vossen
authors.forename: Iris
authors.initials: I
authors.lastname: van der Velde
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
authors.forename: Bart C H
authors.initials: BC
authors.lastname: van der Nagel
authors.forename: Birgit C P
authors.initials: BC
authors.lastname: Koch
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Vulto
authors.forename: Lidwien M
authors.initials: LM
authors.lastname: Hanff
mesh_terms: D000284:Administration, Oral; D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D012996:Solutions; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D002121:Calcium Channel Blockers; D012996:Solutions; D013607:Tablets; D017311:Amlodipine