title: Evaluation of Levothyroxine Bioavailability after Oral Administration of a Fixed Combination of Soy Isoflavones in Post-menopausal Female Volunteers.
abstract: BACKGROUND
  Post-menopausal women under treatment with levothyroxine for their medical conditions may take concomitantly dietary supplements containing soy isoflavones in combination to treat their post-menopausal symptoms. The aim of this study was to investigate the effect of a fixed combination of soy isoflavones on the oral bioavailability of levothyroxine in post-menopausal female volunteers.
  
  
  METHODS
  12 healthy post-menopausal female, who were on stable oral levothyroxine as replacement/supplementation therapy for hypothyroidism, received a single recommended oral dose of a food supplement containing 60 mg of soy isoflavones (>19% genistin and daidzin) concomitantly with (test) and 6 h later (reference) the administration of levothyroxine in a randomized, open label, crossover fashion. Plasma concentrations of levothyroxine and soy isoflavones (daidzin, daidzein, genistin, genistein, S-equol) were determined by LC-MS/MS. Pharmacokinetic (PK) parameters were determined by non-compartmental analysis. No effect of soy isoflavones was assumed if the 90% confidence intervals (CIs) for the estimated ratio test/reference was included in the acceptance limits 0.80-1.25 for PK parameters Cmax and AUCt.
  
  
  RESULTS
  The test/reference ratios Cmax and AUCt of levothyroxine were very close to unity (1.02 and 0.99, respectively) and the corresponding 90% CIs (0.99-1.04 and 0.88-1.12, respectively) fell entirely within the acceptance bioequivalence limits.
  
  
  CONCLUSIONS
  The combination of soy isoflavones used in the present investigation does not affect the rate and extent of levothyroxine absorption when administered concomitantly in post-menopausal women.
authors.affiliation: Rottapharm Biotech S.r.l., Monza, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Persiani
authors.affiliation: Rottapharm Biotech S.r.l., Monza, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Sala
authors.affiliation: Rottapharm Biotech S.r.l., Monza, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Manzotti
authors.affiliation: Rottapharm Biotech S.r.l., Monza, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Colovic
authors.affiliation: Rottapharm Biotech S.r.l., Monza, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zangarini
authors.affiliation: Eurofins|OPTIMED Clinical Research, Gieres, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Donazzolo
authors.affiliation: Rottapharm Biotech S.r.l., Monza, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Barbetta
authors.affiliation: Rottapharm Biotech S.r.l., Monza, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Vitalini
authors.affiliation: Rottapharm Biotech S.r.l., Monza, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Giacovelli
authors.affiliation: Rottapharm S.p.A., Monza, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Benvenuti
authors.affiliation: Rottapharm Biotech S.r.l., Monza, Italy.
authors.forename: L C
authors.initials: LC
authors.lastname: Rovati
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D018592:Cross-Over Studies; D019587:Dietary Supplements; D060754:Equol / Q000097:blood; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage* / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D013025:Glycine max / Q000378:metabolism*; D013810:Therapeutic Equivalency; D013974:Thyroxine / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D007529:Isoflavones; C040641:genistin; C013908:daidzin; D060754:Equol; C004742:daidzein; D013974:Thyroxine