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01-02-2020 | Levothyroxine | Letter to the Editor

Comment on: “Why Were More Than 200 Subjects Required to Demonstrate the Bioequivalence of a New Formulation of Levothyroxine with an Old One?”

Author: Patrick Nicolas

Published in: Clinical Pharmacokinetics | Issue 2/2020

Excerpt

In their article, Concordet et al. [1] deliver a second set of criticisms against the study by Gottwald-Hostalek et al. [2]. In this letter, I would like to challenge this additional argumentation that has already reboosted sensational headlines about the French ‘Levothyrox^® scandal’. …

The reference [13] quoted by Concordet et al. does not contain such data.

Concordet D, Gandia P, Montastruc J-L, Bousquet-Melou A, Lees P, Ferran A, Toutain P-L. Why were more than 200 subjects required to demonstrate the bioequivalence of a new formulation of Levothyroxine with an old one? Clin Pharmacokinet. Epub 21 Aug 2019. https://doi.org/10.1007/s40262-019-00812-x.

Gottwald-Hostalek U, Uhl W, Wolna P, Kahaly GJ. New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials. Curr Med Res Opin. 2017;33:169–74.CrossRef

Nicolas P. Comment on: “Levothyrox^® new and old formulations: are they switchable for millions of patients? Clin Pharmacokinet. 2019;58:959.CrossRef

Yu LX. Quality and bioequivalence standards for narrow therapeutic index drugs. GPhA 2011 Fall Technical Workshop. Available at: https://www.fda.gov/media/82940/download. Accessed 22 Sep 2019.

Munk A. Connections between average and individual bioequivalence. Stat Med. 2000;19:2843–54.CrossRef

Chow S-C., Endrenyi L, Chi E, Yang L-L., Tothfalusi L. Statistical issues in bioavailability/bioequivalence studies. J Bioequiv Availab. 2011;S1. https://doi.org/10.4172/jbb.s1-007.

Yu Y, Teerenstra S, Neef C, Burger D, Maliepaard M. A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials. Br J Clin Pharmacol. 2015;81(4):667–78.CrossRef

Di Girolamo G, Keller GA, de los Santos AR, Schere D, Gonzalez CD. Bioequivalence of two levothyroxine tablet formulations without and with mathematical adjustment for basal thyroxine levels in healthy Argentinian volunteers: a single-dose, randomized, open-label, crossover study. Clin Ther. 2008;30(11):2015–2023.

Levothyroxine (as sodium). EU-procedure number: NL/H/2567/001-004/DC, 2014. Available at: https://www.geneesmiddeleninformatiebank.nl/Pars/h111900.pdf. Accessed 22 Sep 2019.

10.

Australian public assessment report for thyroxine sodium, 2014. Available at: https://www.tga.gov.au/sites/default/files/auspar-thyroxine-sodium-140612.pdf. Accessed 22 Sep 2019.

11.

Levothyroxine sodium soft capsules. Procedure number DE/H/2580/01-12/DC, 2011. Available at: http://mri.cts-mrp.eu/download/DE_H_2580_011_PAR.pdf. Accessed 22 Sep 2019.

12.

Levothyroxine sodium. Procedure NL/H/2700/001-011/DC, 2015. Available at: https://db.cbg-meb.nl/Pars/h112415.pdf. Accessed 22 Sep 2019.

13.

Levothyroxine sodium. UK Licence no. PL00289/1971-73, 2016. http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con738143.pdf. Accessed 22 Sep 2019.

14.

Tanguay M, Girard J, Scarci C, Mautone G, Larouche R. Pharmacokinetic and comparative bioavailability of a levothyroxine sodium oral solution and soft capsule. Clin Pharmacol Drug Dev. 2019;8(4):521–8.CrossRef

Title: Comment on: “Why Were More Than 200 Subjects Required to Demonstrate the Bioequivalence of a New Formulation of Levothyroxine with an Old One?”
Author: Patrick Nicolas
Publication date: 01-02-2020
Publisher: Springer International Publishing
Keyword: Levothyroxine
Published in: Clinical Pharmacokinetics / Issue 2/2020
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-019-00849-y

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