- Design
- Open-label randomised parallel-group single-dose pilot
- Population
- 15 patients with hypothyroidism after total thyroidectomy
- Primary outcome
- Relative bioavailability (AUC, Cmax)
- Effect
- AUC0–∞ GMR 1.28 (90% CI 0.85–1.94); not significant
A British Journal of Clinical Pharmacology pilot randomised 15 newly hypothyroid patients after total thyroidectomy to a single 700 µg dose of levothyroxine given sublingually or orally, fasting, and compared pharmacokinetics.
Total exposure was about 28% higher sublingually (geometric mean ratio 1.28, 90% CI 0.85–1.94), and early exposure about 12% higher, but neither difference was statistically significant. Elimination was the same by both routes.
Oral levothyroxine absorption is affected by food, coffee, proton pump inhibitors and gut disease, and the fasting requirement is a common reason for poor control. A sublingual route could avoid some of that.
With seven and eight patients per arm and a single dose, this is a hypothesis, not evidence for practice. Keep to standard oral dosing.
- Keep to oral levothyroxine taken on an empty stomach as standard
- Check timing with food, coffee, calcium, iron and proton pump inhibitors when control is poor
- Do not switch patients to sublingual levothyroxine on this pilot evidence
Why it matters
The fasting rule for levothyroxine is a real adherence problem, which is why alternatives are being studied.
Don't overread it
Fifteen patients and a single dose: no difference was statistically shown.
The statistics, in plain English
Bioequivalence usually requires the 90% CI of the ratio to sit within 0.80–1.25; here it ran from 0.85 to 1.94, so the routes cannot be called equivalent or different.
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