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A Study in Normal Human Volunteers to Compare the Rate and Extent of Levothyroxine Absorption from Synthroid® and Levoxine®
Author(s) -
Berg Jeffrey A.,
Mayor Gilbert H.
Publication year - 1992
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127009203201213
Subject(s) - cmax , bioavailability , medicine , levothyroxine , pharmacokinetics , bioequivalence , absorption (acoustics) , absorption rate , pharmacology , mathematics , chromatography , chemistry , hormone , materials science , composite material
Numerous branded and generic formulations of levothyroxine (LT4) sodium tablets are currently available. Results from previous studies attempting to examine the comparative bioavailability of these formulations are difficult to interpret because of subject heterogeneity, single time‐point blood sampling, varying degrees of hypothyroidism, and other factors. This study was devised to compare the rate and extent of absorption of LT4 from different LT4 sodium tablet formulations, in a simple model using a single‐dose two‐way single‐blind, randomized cross‐over design in 30 normal, healthy, nonpregnant, female subjects. This design controlled for many factors that limited previous LT4 bioavailability studies. Subjects were given a single 600 fig dose of LT4 as either Synthroid (Boots Pharmaceuticals, Inc., Lincolnshire, IL) tablets (formulation A) or Levoxine tablets (Daniels Pharmaceuticals, St. Petersburg, FL; formulation B). Measurements of baseline‐corrected total T4 serum concentrations determined at multiple time points demonstrated statistically significant differences between the two formulations at the 1.00, 3.00, 5.00, and 18.00 hour sampling times. Statistically significant differences for area under the curve (AUC) (0 to 48 hours) (formulation A, 159.9 ± 9.4 fig‐hour/dL; formulation B, 193.4 ± 10.1 μg‐hour/dL) and maximum peak plasma concentration (Cmax) (formulation A, 5.91 ± .34; formulation B, 7.12 ± .32) also were demonstrated. Furthermore, the ratio of the baseline‐corrected total T4 concentrations (B/A × 100) were 120.9% for AUC and 120.5% for Cmax. These data demonstrate that the administration of Synthroid and Levoxine result in a significantly different rate and extent of absorption of LT4, and therefore these two formulations cannot be considered bioequivalent. Interchange between these products can be expected to produce a different serum T4 concentration.