Levothyroxine soft capsules demonstrate bioequivalent pharmacokinetic exposure with the European reference tablets in healthy volunteers under fasting conditions
Abstract
OBJECTIVE: To assess the bioequivalence (BE) potential under fasting conditions between levothyroxine soft capsules and the European reference tablet formulation. METHODS: Two studies were conducted to assess the BE potential as per European regulations. Study 1 was a two-way crossover BE study comparing a high strength of levothyroxine soft capsules versus levothyroxine tablets (200 μg), while study 2 was a three-way crossover dosage form proportionality study between low, medium, and high strengths of soft capsules. 70 healthy adult subjects participated in the two studies. Each treatment consisted of a 600-μg dose of levothyroxine sodium, administered under fasting conditions. Blood samples were collected for levothyroxine (T4) assay prior to dosing and up to 72 hours post dose. A washout of 35 days separated treatments in each study. Pharmacokinetics was assessed using noncompartmental methods. RESULTS: A total of 61 subjects completed the studies. Baseline-adjusted total T4 ratios (test/reference) and 90% confidence intervals (CIs) between soft capsules and tablets were within 80.00 - 125.00%. Comparison of the three strengths of soft capsules indicated pharmacokinetic equivalence between them (ratios and 90% CIs were contained within 80.00 - 125.00%). Overall, levothyroxine sodium was well tolerated with all products when given as single oral doses of 600 μg, except for 1 serious adverse event of secondary bacteremia reported in study 2, deemed not to be related to treatment. CONCLUSION: Levothyroxine soft capsules meet BE criteria in terms of systemic exposure when compared to a European reference tablet under fasting conditions in healthy volunteers.
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Bioequivalence between solid and liquid preparations has been confirmed in crossover clinical trials.
“Bioequivalence between solid and liquid preparations has been confirmed in crossover clinical trials (183–185).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [183]
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- Authors
- Al-Numani, D., Scarsi, C., & Ducharme, M. P.
- Venue
- Int. Journal of Clinical Pharmacology and Therapeutics
- Publisher
- Dustri-Verlgag Dr. Karl Feistle
- Published
- 2016-02-01
- Volume
- 54
- Issue
- 02
- Pages
- 135-143
- ISSN
- 0946-1965 (ISSN-L)
- OpenAlex
- W2460339062
- Cited by
- 12
- References
- 0
- Citations by year
- 2025: 2 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Clinical Pharmacology and Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- levothyroxine, bioequivalence, pharmacokinetics, fasting conditions, thyroxine, healthy volunteers, adverse events, bacteremia
- MeSH terms
- Adult, Capsules, Fasting, Female, Humans, Male, Tablets, Therapeutic Equivalency, Thyroxine, Cross-Over Studies, Healthy Volunteers
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