Comparative bioavailability of sublingual vs . oral levothyroxine in patients with post‐thyroidectomy hypothyroidism: A single‐dose pilot study
Osama Shoaip, Mahmoud Bassiony, Rana Elbayar, Mohanned Mohsen, Hagar Elhammady, Rawda Elsaadany, Nehal M. RamadanAbstract
Aim
To evaluate the relative bioavailability of sublingual vs . oral levothyroxine (L‐T4) in post‐thyroidectomy patients, aiming to overcome gastrointestinal absorption variability.
Methods
This open‐label, randomized, parallel‐group pilot study enrolled 15 de novo hypothyroid patients following total thyroidectomy (oral: n = 7, sublingual: n = 8). Participants received a single 700‐μg L‐T4 dose under fasting conditions. Pharmacokinetic parameters, including baseline‐corrected AUC, Cmax and Tmax, were determined via noncompartmental analysis.
Results
Sublingual administration resulted in a Geometric Mean Ratio (GMR) of 1.283 (90% CI: 0.849–1.938) for total systemic exposure (AUC 0–∞ ) and 1.123 (90% CI: 0.815–1.547) for early exposure (AUC 0–48 ) compared to the oral route. Due to the small sample size and inter‐subject variability, these differences did not reach statistical significance. Elimination kinetics ( T 1/2 , MRT) were route‐independent, while sublingual delivery showed lower apparent clearance (CL/ F ), supporting improved bioavailability.
Conclusion
Sublingual L‐T4 achieved numerically higher systemic exposure with comparable elimination kinetics to the oral route. These findings suggest sublingual delivery is a promising, practical alternative that mitigates fasting constraints. Large‐scale crossover studies are needed to definitively establish bioequivalence and long‐term efficacy.