title: Timing of breakfast does not influence therapeutic efficacy of liquid levothyroxine formulation.
abstract: Oral levothyroxine (L-T4) is the mainstay of hypothyroidism treatment. Many factors may influence its absorption, including the timing of administration. Objective of the study is to demonstrate the therapeutic equivalence of administering liquid L-T4 with breakfast or 10 min before breakfast. This was a pilot study conducted with a crossover design AB/BA where A stays for L-T4 with breakfast and B for L-T4 10 min before breakfast. A post hoc analysis was conducted to compare L-T4 administered at breakfast or 10 min before breakfast with L-T4 administered 30 min before breakfast. Sixty-one hypothyroid patients were enrolled and assigned to one of the two treatment sequences. All patients were evaluated for TSH levels at the end of each period. Fifty-nine patients completed the study. The mean thyrotropin concentration was 1.52 ± 0.73 µU/ml when L-T4 was administered with breakfast and 1.46 ± 0.81 µU/ml when it was taken 10 min before breakfast, without clinically and statistically significant differences (P = 0.59), regardless of treatment sequence and period. The mean thyrotropin concentration was 1.54 ± 0.9 µU/ml when L-T4 was administered at 0-10 min intervals before breakfast and 1.25 ± 0.7 µU/ml when it was taken 30 min before breakfast (ratio = 1.23, within our definition of equivalence set at 0.8-1.25). There is therapeutic equivalence between liquid L-T4 administration at breakfast or 10 min before breakfast. We can also hypothesize that there are no clinically relevant differences between liquid L-T4 administration 30 min before breakfast or at shorter intervals.
authors.affiliation: Department of Medicine, University of Perugia, Perugia, Italy.|Research Centre of Thyroid Proteomics and Genomics (CRiProGeT), University of Perugia, Terni, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morelli
authors.affiliation: Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Reboldi
authors.affiliation: Department of Medicine, University of Perugia, Perugia, Italy.|Research Centre of Thyroid Proteomics and Genomics (CRiProGeT), University of Perugia, Terni, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Moretti
authors.affiliation: Department of Medicine, University of Perugia, Perugia, Italy.|Research Centre of Thyroid Proteomics and Genomics (CRiProGeT), University of Perugia, Terni, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Menicali
authors.affiliation: Research Centre of Thyroid Proteomics and Genomics (CRiProGeT), University of Perugia, Terni, Italy.|Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Avenia
authors.affiliation: Department of Medicine, University of Perugia, Perugia, Italy. efisio.puxeddu@unipg.it.|Research Centre of Thyroid Proteomics and Genomics (CRiProGeT), University of Perugia, Terni, Italy. efisio.puxeddu@unipg.it.
authors.forename: Efisio
authors.initials: E
authors.lastname: Puxeddu
mesh_terms: D000328:Adult; D000368:Aged; D062408:Breakfast; D018592:Cross-Over Studies; D004339:Drug Compounding; D004435:Eating / Q000502:physiology*; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012996:Solutions; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage*; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood; D055815:Young Adult
chemical_list: D012996:Solutions; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine
keywords: Hypothyroidism; Levothyroxine; Oral solution; Replacement therapy; TSH; Therapeutic equivalence