CoChat
Sign Up
Cited by 185Thyroid Disorders and TreatmentsPharmaceutical Economics and PolicyBiosimilars and Bioanalytical Methods

Bioequivalence of Generic and Brand-name Levothyroxine Products in the Treatment of Hypothyroidism

Dong, Betty J.·1997·JAMA: The Journal of the American Medical Association
DOI 10.1001/jama.1997.03540390035032
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1001/jama.1997.03540390035032

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Mayor et al. reanalysis found LT4 products that seemed pharmacokinetically bioequivalent were not therapeutically equivalent.

    “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]

  • Dong et al. concluded two proprietary and two generic LT4 products were bioequivalent and therapeutically equivalent.

    “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]

Cites

Flagged first, then by citations

1 of the 24 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

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
DOI
10.1001/jama.1997.03540390035032
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review