Before going any further, this research was sponsored IBSA - who are behind the Tirosint product.
There are many here who would agree that there appear to be differences between makes of levothyroxine. If we accept that the products contain the same amount of levothyroxine, we do need another explanation as to why.
The paper suggests stomach acidity. I am not convinced. I suspect it is the alkalinity in the intestine. After all, levothyroxine is more soluble in alkaline than acidic or neutral water solutions. But if the maximum alkalinity is dependent on how acidic the stomach is, then the two could very well go hand in glove with each other.
Also, could the amount of levothyroxine that is not absorbed be one of the causes of problems lower down the intestinal tract? That is, if we absorbed 100% of the levothyroxine, we'd not have gut issues. Many seem to absorb about 80% and have some gut issues. Perhaps those who only absorb 60 to 70% have the worst gut issues? (Only trying to think through why a well-absorbed gel cap would actually be different to an indifferently or poorly absorbed tablet.)
J Pharm Pharm Sci. 2015;18(5):844-55.
When Bioequivalence in Healthy Volunteers May not Translate to Bioequivalence in Patients: Differential Effects of Increased Gastric pH on the Pharmacokinetics of Levothyroxine Capsules and Tablets.
Seng Yue C1, Benvenga S, Scarsi C, Loprete L, Ducharme MP.
1 Learn and Confirm Inc., St-Laurent, Quebec, Canada...
Clinical studies have suggested that proton pump inhibitors may decrease levothyroxine absorption and an in vitro study suggested that the effect of pH on dissolution may differ with formulation. To determine the impact of formulation on the pharmacokinetics of levothyroxine in altered gastric pH conditions, this study compared the pharmacokinetics of levothyroxine capsules and tablets, two formulations deemed bioequivalent in healthy volunteers under fasting conditions, when taken with or without esomeprazole.
Two clinical studies were conducted in healthy volunteers given single dose levothyroxine (600 mg) with a 45-day washout period. In Study 1 (parallel-design/two-way crossover), 16 subjects received either levothyroxine capsules or tablets, each group with or without prior administration of intravenous esomeprazole (maximum dose of 80 mg). In Study 2 (two-way crossover), 16 subjects received both capsules or tablets after intravenous esomeprazole. Blood samples were collected pre-dose and up to 24 hours post-dose. Baseline-adjusted pharmacokinetic parameters were calculated: Cmax (maximal concentration), Tmax (time to Cmax), AUC0-t (area under the concentration-time curve from 0 to the last detectable concentration), AUC0-6 and AUC0-12 (areas under the curve from 0 to 6 and 12 hours, respectively). Analyses of variance were conducted to compare ln-transformed Cmax and AUC. Non-parametric Tmax analyses were done.
In Study 1, esomeprazole caused a greater decrease in overall levothyroxine exposure of tablets vs. capsules (13% vs 6% for Cmax, 18% vs. 14% for AUC(0-6), 17% vs. 5% for AUC(0-12) and 10% vs. 8% for AUC(0-t)). In Study 2 esomeprazole administration resulted in a 16% smaller levothyroxine exposure with tablets vs. capsules. No statistically significant differences in Tmax were found.
Although both formulations are considered "bioequivalent" in healthy volunteers, they may not necessarily be bioequivalent in patients with impaired gastric pH conditions. Levothyroxine capsules may therefore be more appropriate for patients with decreased gastric acidity.
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Updated 8th July 2017: The paper contains an obvious typo - that I had missed. It says (600 mg) where it should be (600 mcg) or, preferably (600 micrograms). Is it somewhat concerning that the experts can't get it right.