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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/8542

Title: Including information on the therapeutic window in bioequivalence acceptance
Authors: Jacobs, Tom
De Ridder, Filip
Rusch, Sarah
Van Peer, Achiel
Molenberghs, Geert
Bijnens, Luc
Issue Date: 2008
Citation: PHARMACEUTICAL RESEARCH, 25(11). p. 2628-2638
Abstract: Purpose. A novel bioequivalence limit is proposed taking into account the therapeutic window. Methods. The therapeutic range is introduced as the ratios maximum tolerated dose/therapeutic dose (MTD/D) and the therapeutic dose/lowest effective dose. The performance of the new acceptance range was compared with the methods of Schuirmann and Karalis. The method was retrospectively applied to data of three drugs with a narrow therapeutic window (phenytoin, theophylline and digoxin). Results. Simulations and examples show that the resulting bioequivalence limits are (1) narrow for narrow-index drugs, (2) expanded for highly variable drugs with a wide therapeutic window and (3) similar to the classical limits for less variable drugs with a wide therapeutic range. Conclusions. The approach has the desirable property of resulting in a more narrow acceptance range for doses near the boundaries of the therapeutic window and a wider acceptance range for products with a broad therapeutic window.
Notes: [Jacobs, Tom; Molenberghs, Geert] Univ Hasselt, Interuniv Inst Biostat & Stat Bioinformat, B-3590 Diepenbeek, Belgium. [De Ridder, Filip; Rusch, Sarah; Van Peer, Achiel; Bijnens, Luc] Johnson & Johnson Pharmaceut Res & Dev, B-2340 Beerse, Belgium. [Molenberghs, Geert] Katholieke Univ Leuven, Int Inst Biostat & Stat Bioinformat, B-3000 Leuven, Belgium.
URI: http://hdl.handle.net/1942/8542
DOI: 10.1007/s11095-008-9680-6
ISI #: 000259742300017
ISSN: 0724-8741
Category: A1
Type: Journal Contribution
Validation: ecoom, 2009
Appears in Collections: Research publications

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