Comparative pharmacokinetic and pharmacodynamic evaluation of branded and generic formulations of meloxicam in healthy male volunteers

Abstract

PurposeThe primary aim of the present study was to assess the pharmacokinetic bioequivalence between a generic formulation of meloxicam 15 mg tablets (Meloxicam Hexal) and its respective brand product (Mobic), in order to verify whether the generic product conforms to the regulatory standards of bioequivalence in the postmarketing setting. As a secondary exploratory aim, the pharmacodynamic effects of the two formulations were also evaluated by means of rating scales following hyperalgesia induced by cutaneous freeze injury.Subjects and methodsA single 15 mg dose of generic or branded meloxicam tablets was administered to 24 healthy male volunteers in a crossover fashion. Plasma samples, collected for 24 hours after dosing, were assayed for meloxicam concentration by a validated highperformance liquid chromatography method.ResultsThe analysis of pharmacokinetic parameters did not show any significant difference between the two meloxicam formulations: the 90% confidence intervals fell within the acceptance range of 80%–125% (0.84–1.16 for area under the curve [0–24], and 0.89–1.23 for peak concentration). No difference in the pharmacodynamic end point was observed between the two groups.ConclusionThe pharmacokinetic profiles of the two meloxicam formulations confirm the regulatory criteria for bioequivalence; pharmacodynamic data indicate a similar antihyperalgesic effect. The two formulations can be used interchangeably in the clinical setting.

Pharmacokinetics of Meloxicam Tablets in Healthy Chinese Adults in the Fasting and Fed States: A Single‐Site, Single‐Dose, Randomized, Open, 2‐Period, 2‐Sequence, Crossover Bioequivalence Study

“…In recent years, increasing attention has been paid to the PK of meloxicam. 16,17 However, few studies have been performed in Chinese HVs. 18,19 This study, with fasting and fed arms, was performed to investigate the BE of meloxicam from 2 manufacturers.…”

Sampling times and genotyping concerns in bioequivalence evaluation of branded and generic formulations

“…2 The total sampling points (not including predose) should not be less than twelve. 3 However, only eight blood samples, after dosing, per subject were taken in the study by Del Tacca et al 1 The duration of sampling is usually at least three times the terminal half-life (t 1/2 β ) of the measured compound for immediate-release products. 3 However, a sampling period longer than 72 hours is not considered necessary for any immediate release formulation irrespective of the half-life of the drug.…”

“…Meloxicam AUC (0–t) covered only 55.6% of the AUC (0–inf) , which was not in accordance with the criteria (≥80%) established by European Medicines Agency (EMA) guidelines. Although this article notes that the main study objective is not to investigate the complete PK profiles of meloxicam in healthy volunteers but rather to compare PK and PD patterns between branded and generic meloxicam, the results of bioequivalence evaluation would be more convincing if the industry guideline was well followed, especially regarding that the lower limit of quantification (LLOQ) for the analytical method established by Del Tacca et al 1 has met the criteria of EMA (ie, higher than 1/20 of maximum concentration [C max ]). 2…”

“…We read with great interest the study by Del Tacca et al, 1 who performed a comparative pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of branded and generic formulations of meloxicam in healthy male subjects, and concluded that the two products can be used interchangeably in clinical practice. We especially appreciate their exploratory study on the PD/PK relationship which provides an important reference for bioequivalence studies of analgesics.…”

“…We thank Zhao et al for their interest in our clinical research article on the post-marketing evaluation of the bioequivalence between generic and branded formulations of meloxicam, recently published in Therapeutic and Clinical Risk Management . 1 …”