title: Pharmacokinetic equivalence of a levothyroxine sodium soft capsule manufactured using the new food and drug administration potency guidelines in healthy volunteers under fasting conditions.
abstract: OBJECTIVE
  To assess the pharmacokinetic equivalence of a new soft capsule formulation of levothyroxine versus a marketed reference product and to assess the soft capsule formulated with stricter potency guidelines versus the capsule before the implementation of the new potency rule.
  
  
  METHODS
  Two single-dose randomized two-way crossover pharmacokinetic equivalence studies and one dosage form proportionality single-dose study comparing low, medium, and high strengths of the new formulation. All three studies were performed in a clinical setting. Participants were healthy male and female adult subjects with normal levothyroxine levels. A total of 90 subjects participated in the three studies.
  
  
  RESULTS
  Pharmacokinetic parameters were calculated on baseline- adjusted concentrations. The first pharmacokinetic equivalence study compared the levothyroxine sodium soft capsule formulation (Tirosint) with the reference Synthroid tablets and the two products were considered bioequivalent. The dosage form proportionality study compared the 50-, 100-, and 150-μg test capsules strengths dosed at the same level (600 μg) and all three strengths were considered equivalent when given at the same dosage. The last study compared the test capsule used in the first two studies with a new capsule formulation following the new potency guideline (±5%) set forward by the Food and Drug Administration and the two capsules were considered bioequivalent. Doses were well tolerated by subjects in all three studies with no serious adverse events reported.
  
  
  CONCLUSIONS
  The levothyroxine soft capsule formulated with the stricter new potency guideline set forward by the Food and Drug Administration met equivalence criteria in terms of rate and extent of exposure under fasting conditions to the reference tablet formulation. Clinical doses of the capsule formulation can be given using any combination of the commercialized strengths.
authors.affiliation: Faculté de Pharmacie, University of Montreal, Montreal, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Colucci
authors.forename: Pina
authors.initials: P
authors.lastname: D'Angelo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mautone
authors.forename: Claudia
authors.initials: C
authors.lastname: Scarsi
authors.forename: Murray P
authors.initials: MP
authors.lastname: Ducharme
mesh_terms: D000328:Adult; D002214:Capsules / Q000008:administration & dosage / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D004304:Dosage Forms; D005215:Fasting / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D013607:Tablets / Q000008:administration & dosage / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency; D013974:Thyroxine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D002214:Capsules; D004304:Dosage Forms; D013607:Tablets; D013974:Thyroxine