Comparison of average, scaled average, and population bioequivalence methods for assessment of highly variable drugs: An experience with doxifluridine in beagle dogs

Title
Comparison of average, scaled average, and population bioequivalence methods for assessment of highly variable drugs: An experience with doxifluridine in beagle dogs
Author(s)
강원구백인환[백인환]이병요[이병요]권광일[권광일]
Keywords
INDIVIDUAL BIOEQUIVALENCE; PRODUCTS; LIMITS; BIOAVAILABILITY; CROSSOVER; DESIGN
Issue Date
201001
Publisher
ELSEVIER SCIENCE BV
Citation
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, v.39, no.1-3, pp.175 - 180
Abstract
Several strategies for overcoming the challenge of establishing bioequivalence (BE) for highly variable drugs (HVDs; drugs having within-subject variability >0.3) have been considered in recent years. Within-subject variability of the area under the curve (AUC(4h)) and peak concentration (C(max)) of doxifluridine in the minimal group (n=24) were 0.444 and 0.491, respectively, meeting the criteria for an HVD. For the large group (n=60), within-subject variability of the AUC(4h) and C(max) were 0.431 and 0.493, respectively. The 90% confidence interval for the AUC(4h) and C(max) of the ratio of the test drug to the reference drug exceeded the acceptable BE limits (0.80-1.25) of the ABE (average bioequivalence), in both the minimal and large groups. However, the 90% Cl fell within the extended BE limits (0.61-1.64) of the SABE (scaled average bioequivalence), calculated using within-subject variability. The 95% CI of the AUC(4h) and C(max) the ratio of test to reference drug were within the extended BE limit (<1.73) of the PBE (population bioequivalence), calculated using total variance. Our results suggest that the SABE method may be useful for evaluating the BE of HVDs and for meeting the need for international guidelines for BE. (C) 2009 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/22984http://dx.doi.org/10.1016/j.ejps.2009.11.013
ISSN
0928-0987
Appears in Collections:
약학대학 > 약학부 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE