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.
Keywords: Hypothyroidism; Levothyroxine; Oral solution; Replacement therapy; TSH; Therapeutic equivalence.