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Abstract
Background: The proprietary form of topiramate is indicated in Mexico as an antiepileptic agent
and in the prophylaxis of migraine headaches. However, before generic topiramate is
placed on the market, pharmacokinetic studies investigating the bioequivalence of
generic and branded formulations are needed.
Objective: The aim of this study was to compare the bioequivalence and tolerability of a generic
(test) and a branded (reference) formulation of topiramate 100 mg in healthy Mexican
volunteers.
Methods: This open-label, randomized-sequence, 2-period crossover study was conducted at Ipharma
SA de CV, Monterrey, Mexico. Eligible subjects were healthy male Mexican volunteers
aged 18 to 45 years. Participants were randomly assigned to receive 100 mg of the
test or reference formulation, followed by a 3-week washout period and administration
of the alternate formulation. Doses were administered after a 12-hour overnight fast.
For analysis of pharmacokinetic properties, including Cmax, AUC0-t, and AUC0-∞, blood samples were obtained over a 144-hour period after dosing. The formulations
were to be considered bioequivalent if calculations of a 90% CI for the ratio of the
means of the measures for the test and reference formulations fell within bioequivalence
limits, 80% to 125%, for logarithmic (log) transformation of Cmax and AUC, and if two 1-sided t tests showed P < 0.05. Tolerability was assessed using vital sign measurement (blood pressure, body
temperature, heart rate, and respiratory rate), laboratory analysis (hematology, blood
biochemistry, hepatic function, and urinalysis), and subject interview.
Results: Twenty-eight men (mean age, 22.21 years [range, 18–28 years]; mean weight, 75.04
kg [range, 62–96 kg]; mean height, 177 cm [range, 163–192 cm]) were enrolled in this
study, and 28 (14 each randomized to receive the test or reference formulation first)
completed it. No period or sequence effects were observed. The 90% CIs for the log-transformed
Cmax, AUC0-t and AUC0-∞ were 94.70 to 112.05, 98.88 to 105.16, and 98.80 to 105.28, respectively (all, P < 0.05). No adverse events were reported by the volunteers or found on clinical laboratory
testing during the study.
Conclusions: This study did not find any statistically significant differences in Cmax or AUC values between the test and reference formulations of oral topiramate 100
mg in this population of healthy adult male Mexican volunteers. On that basis, and
according to both the rate and extent of absorption, the test and reference formulations
met the regulatory criteria for bioequivalence. Both formulations were well tolerated.
Key words:
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Article info
Publication history
Accepted:
December 10,
2008
Identification
Copyright
© 2009 Excerpta Medica Inc. All rights reserved. Published by Elsevier Inc.
