FAILURE OF STATISTICAL METHODS TO
PROVE BIOEQUIVALENCE OF MELOXICAM
DRUG PRODUCTS. I. PARAMETRIC METHODS
ANCA VĂTĂŞESCU1, FLORIN ENACHE2, CONSTANTIN
MIRCIOIU1, DALIA SIMONA MIRON1, ROXANA SANDULOVICI3
1Carol Davila University of Medicine & Pharmacy, Bucharest
2Institute of Statistics, Romanian Academy, Bucharest
3Biopharmacy & Pharmacol Res S.A., Bucharest
*corresponding author: ancavatasescu@yahoo.com
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Abstract:

Establishing the bioequivalence (BE) and interchangeability of two drug products is a problem of building a confidence interval (CI) for the ratio of the means for the main pharmacokinetic parameters of the respective drug products.
The paper presents the case of a BE study concerning two suppositories formulations containing meloxicam. Although the conditions for application of parametric test were not fulfilled following a non-normal distribution of pharmacokinetic parameters of the reference drug, it were applied the “official rules” and it were calculated the 90 % confidence intervals for the maximum concentration (Cmax) and the area under the curve (AUC). The result of the statistical test was the rejection of BE. But it appeared that the
tested drug, at least from the fact that it was less variable, was superior to the reference drug. The fact that plasma levels of the tested drug were greater than plasma levels of the reference drug suggested rather a reduced release of active substance from reference formulation than a super-bioavailability. In this conditions, the rejecting of tested drug was considered both incorrect and unfair since the deficiencies appeared all to the reference drug. Simulations showed that BE could be proved only with a large number of subjects, which was considered a non-ethical approach. Application of “ethical” scaled criteria lead to the conclusion that the products are bioequivalent.

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