The DOI matches its Crossref record; 23 of the 24 references it cites were found in a registry or an index.
Bioequivalence of Generic and Brand-name Levothyroxine Products in the Treatment of Hypothyroidism
Abstract
OBJECTIVE: To compare relative bioavailability of Synthroid, Levoxine (Levoxine has been renamed Levoxyl), and 2 generic levothyroxine sodium preparations. DESIGN: Single-blind (primary investigators blinded), randomized, 4-way crossover trial. SETTING: Ambulatory care. PATIENTS: Twenty-two women with hypothyroidism who were clinically and chemically euthyroid and were receiving levothyroxine sodium, 0.1 or 0.15 mg. INTERVENTIONS: All patients received each of the 4 levothyroxine products for 6-week periods in the same dosage as their prestudy regimen with no washout period. The order of the drug sequences was randomly determined before study initiation. MAIN OUTCOME MEASURES: Area under the curve, time to peak serum concentrations, and peak serum concentrations of thyroxine, triiodothyronine, and free thyroxine index for all 4 products. RESULTS: All data analyses were completed prior to unblinding of the product codes. No significant differences between the 4 products were found in area under the curve or peak serum concentrations of total thyroxine, total triiodothyronine, or free thyroxine index. Although Synthroid produced a more rapid rise in total serum triiodothyronine concentration and a higher total peak serum triiodothyronine concentration than the other products, these differences were not statistically significant (P=.08). The Food and Drug Administration criterion for relative bioequivalence within 90% confidence intervals (0.8-1.25) was demonstrated (P<.05) for all pairs of products. Relative bioequivalence of 0.95 to 1.07 was demonstrated, tighter than the current bioequivalence criterion for oral formulations. CONCLUSIONS: The 4 generic and brand-name levothyroxine preparations studied are different but are bioequivalent by current Food and Drug Administration criteria and are interchangeable in the majority of patients receiving thyroxine replacement therapy. Further investigation is required to determine whether our results are equally applicable to all existing levothyroxine preparations.
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“In contrast, Mayor et al. (101) of Knoll pharmaceuticals reanalyzed the data by Dong et al. (100) using correction for baseline T4 levels and the TSH data obtained during the trial, and found that the LT4 products that seemed to be pharmacokinetically bioequivalent were, in fact, not equivalent therapeutically.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [100]
In the citing paper
“Dong et al. (100), in a study sponsored by Knoll Pharmaceuticals, studied the pharmacokinetics profiles of two proprietary LT4 products (one of which has been reformulated since this evaluation) and two generic LT4 products (neither of which is currently available) and also concluded that they were bioequivalent and therapeutically equivalent.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [100]
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Metadata
- Authors
- Dong, B. J.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Dong, Betty J.
- Venue
- JAMA: The Journal of the American Medical Association
- Publisher
- American Medical Association (AMA)
- Published
- 1997-04-16
- Volume
- 277
- Issue
- 15
- Pages
- 1205
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2010621528
- Cited by
- 185
- References
- 24
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 6 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 7 · 2012: 7
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- DigitalGeorgetown (Georgetown University Library) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- levothyroxine, bioequivalence, generic drugs, brand-name drugs, hypothyroidism, thyroxine replacement, triiodothyronine, free thyroxine index, crossover trial
- MeSH terms
- Adult, Aged, Drug Industry, Female, Humans, Hypothyroidism, Middle Aged, Therapeutic Equivalency, Thyroid Function Tests, Thyrotropin, Thyroxine, Triiodothyronine, Drugs, Generic, Cross-Over Studies, Area Under Curve
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