Drug Res (Stuttg) 2016; 66(03): 136-140
DOI: 10.1055/s-0035-1555784
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Evaluation of Levothyroxine Bioavailability after Oral Administration of a Fixed Combination of Soy Isoflavones in Post-menopausal Female Volunteers

S. Persiani
1  Rottapharm Biotech S.r.l., Monza, Italy
,
F. Sala
1  Rottapharm Biotech S.r.l., Monza, Italy
,
C. Manzotti
1  Rottapharm Biotech S.r.l., Monza, Italy
,
M. Colovic
1  Rottapharm Biotech S.r.l., Monza, Italy
,
M. Zangarini
1  Rottapharm Biotech S.r.l., Monza, Italy
,
Y. Donazzolo
2  Eurofins|OPTIMED Clinical Research, Gieres, France
,
B. Barbetta
1  Rottapharm Biotech S.r.l., Monza, Italy
,
C. Vitalini
1  Rottapharm Biotech S.r.l., Monza, Italy
,
G. Giacovelli
1  Rottapharm Biotech S.r.l., Monza, Italy
,
C. Benvenuti
3  Rottapharm S.p.A., Monza, Italy
,
L. C. Rovati
1  Rottapharm Biotech S.r.l., Monza, Italy
› Author Affiliations
Further Information

Publication History

received 20 April 2015

accepted 11 June 2015

Publication Date:
30 June 2015 (online)

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.

Conclusion: 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.