Results of a bioavailability, crossover study suggest use of proton pump inhibitors did not interfere with the absorption of levothyroxine sodium oral solution.
New research suggests the absorption of levothyroxine sodium oral solution (Tirosint-SOL) was not affected by concomitant use of proton pump inhibitors (PPIs).
Presented at the American Thyroid Association (ATA)’s 90th Annual Meeting, results of the 3-way crossover study demonstrate the novel formulation of levothyroxine was not influenced by use of omeprazole.
"Unlike traditional levothyroxine tablets whose dissolution and subsequent absorption are affected by the presence of acid-reducing agents, Tirosint-SOL does not need to dissolve before being absorbed and may be taken regardless of stomach acidity," said Murray Ducharme, PharmD, associate professor of Clinical Pharmacology and Pharmacometrics at the University of Montreal, in a statement. "These study results suggest that the presence of a powerful and long-lasting stomach acid-reducing PPI drug such as omeprazole, regardless of the timing of administration, has no effect on the bioavailability and absorption of Tirosint-SOL."
With previous data suggesting use of potion pump inhibitors could have a significant effect on the absorption of levothyroxine tablets, clinicians have hypothesized about the potential effects on the absorption of levothyroxine sodium oral solution. With this in mind, the current study was designed by Ducharme and a team of colleagues from the University of Montreal and Virginia Commonwealth University as a single-center, comparative bioavailability, open-label, randomized, single-dose, 3-period, crossover study with a 35-day washout period between treatments.
The study was designed to assess the bioavailability of levothyroxine sodium oral solution when administered as a single dose of 600 micrograms in conjunction with omeprazole compared to levothyroxine sodium oral solution alone. Patients included in the study were placed into 3 groups, with the first group receiving levothyroxine sodium oral solution and omeprazole at the same time in the morning, the second received levothyroxine sodium oral solution in the evening and omeprazole at night, and the third group received levothyroxine sodium oral solution in the morning. Of note, all patients received levothyroxine sodium oral solution in day 5 of the study period.
In total, 36 patients were rolled in the study. At the conclusion of the study, 30, 28, and 31 subjects were included in the first, second, and third treatment groups, respectively. Investigators pointed out 45 subjects withdrew voluntarily and 3 did not complete the trial. The patients who did not complete the study failed to do so due to testing positive for COVID-19, not receiving Total T3 laboratory results prior to dosing, and vomiting.
Upon analysis, results for both comparisons suggested geometric mean ratios and confidence intervals for uncorrected and baseline-corrected PK parameters were within predefined equivalence boundaries of 80-125%. A total of 43 treatment-emergent adverse events are reported during the trial. Of these, 20 were possibly related to LT4 and 8 to omeprazole. The frequency of events was 20% for the first treatment group, 39.39% for the second treatment group, and 15.63% for the third treatment group.
"The opportunity to provide patients affected by hypothyroidism with a levothyroxine formulation that is not affected by commonly-used acid-reducing agents like omeprazole may improve the consistency of hypothyroidism therapy,” said Francesco Celi, MD, Chair of the Division of Endocrinology, Diabetes and Metabolism at Virginia Commonwealth University, in the aforementioned statement.
This study, “The Pharmacokinetics of a Novel Solution of Levothyroxine is not Influenced by Proton-Pump Inhibitor,” at ATA 2021.