ESTIMATION OF THERAPEUTIC EQUIVALENCE USING BIOEQUIVALENCE STATISTICAL METHODS FOR ALGOPIRIN TABLETS VERSUS EXCEDRIN ANALGESIC FORMULATIONS
FLORIN ENACHE1, ION MIRCIOIU2, GEORGE CORLAN1, ROXANA SANDULOVICI1, CONSTANTIN MIRCIOIU1
1”Carol Davila” University of Medicine & Pharmacy, Bucharest
2Biopharmacy & Pharmacol Res S.A., Bucharest
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A clinical study was performed in order to prove the non-inferiority in relieving
headache of a unique dose of treatment using Algopirin®, a fixed combination with
acetylsalicylic acid (ASA, aspirine), acetaminophen, caffeine and clorpheniramine a new
analgesic combination versus Excedrin®, which contains the same active substances but in
much higher doses. Pain intensity was quantified using a Visual Analog Scale (VAS) score
which was established by patients on a 1 – 100 points scale, before and 30 min, 60 min, 120
min, 180 min and 240 min after drug intake.
The clinical trial was a cross-over study with two periods and two sequences,
usual in bioequivalence studies, each subject being its own control. Consequently in this
study were applied specific statistical methods for bioequivalence studies.
The primary endpoint in the statistical evaluation was the Area Under the Pain
For verification of therapeutic equivalence there were applied both parametric
(method of confidence intervals) and non-parametric methods (Wilcoxon-Man Whitney
two one-sided test for bioequivalence, and confidence interval associated with Wilcoxon
signed rank statistic based of Hodges - Lehmann estimator).
If the 90 % confidence interval for ratio of means of areas under curve was
included in the interval 80 – 125 % the products were considered as therapeutically
The results of all applied tests indicated a therapeutic equivalence of the
formulations though amounts of active substances are much lower in Algopirin®.