Oral relative bioavailability of a once-weekly formulation of levothyroxine sodium to a once-daily marketed formulation: a randomized, crossover study

Background: Daily levothyroxine (1.6 mcg/kg/day) is recommended by current guidelines for hypothyroidism. However, difficulty in following stringent administration guidelines affects patient compliance. To tackle this problem, weekly administration of seven times the daily dose is being considered. The current study assesses the relative bioavailability of a once weekly formulation of levothyroxine sodium to a once daily formulation.
Methods: This was an open-label, balanced, randomized, two-treatment, two-sequence, two-period, two-way crossover oral relative bioavailability study. A total of 24 healthy male human subjects were divided into two groups of 12 each and randomized to either weekly or daily treatment with levothyroxine in first period, which were switched between groups in second period after a washout period of 35 days. Cmax and AUC0-168h were calculated as primary pharmacokinetic parameters for T4 and T3. Results: Ratios of least square means of Cmax and AUC0-168h of both formulations for T4 were 105.35% (95% CI- 101.32-109.54%) and 108.65% (104.68-112.78%). For T3, the ratios of Cmax and AUC0-168h were 103.83% (101.47-106.26%) and 103.11% (99.4-106.96%) respectively. All the ratios fell within the accepted bioequivalence limit of 80-125%. Conclusion: Weekly levothyroxine formulation was found to be bioequivalent with daily treatment. Thus, the formulation can be used as an alternative to daily thyroid replacement therapy.