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Bioavailability of a Generic Sustained-Release Formulation of Diclofenac Compared with the Standard Sustained-Release Formulation

  • Pharmacokinetics
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Summary

The aim of this study was to demonstrate the bioequivalence of two 100mg sustained-release formulations of diclofenac sodium: the standard formulation, marketed in France as Voltaren LP®, and 3 different batches of a generic formulation marketed in France as Xenid LP®. The study was an open, randomised, 4-way crossover study with 4 treatment periods separated by a washout interval of at least 7 days. All treatments were safe and well tolerated. The diclofenac pharmacokinetic values for Voltaren LP® were similar to those observed in previous studies, with a mean maximum plasma drug concentration (Cmax) of 1827 ± 1146.5 nmol/L, a median time to reach Cmax (tmax) of 5 hours, and an estimated half-life of 3.0 ± 1.7 hours. The mean area under the plasma concentration-time curve up to the last quantifiable concentration (AUC0–t) for Voltaren LP® was 7154 ± 1556.2 nmol/L·h. Overall diclofenac plasma concentrations were much lower after administration of all batches of Xenid LP® than after administration of Voltaren LP®. The mean relative bioavailability from comparison of AUC0–t values for batches A, B and C of Xenid LP® with those for Voltaren LP® was 79.0 ± 22.6%, 59.3 ± 38.5% and 50.2 ± 17.8%, respectively. Cmax was approximately 60 to 74% lower for all batches of Xenid LP® compared with Voltaren LP®. There was inter- and intrasubject variability in the plasma data for all treatments; however, this was more pronounced after administration of Xenid LP®. Coefficient of variation values ranged from 22 to 67% for AUC0–t and Cmax. Comparison of AUC0–t, Cmax and tmax indicated that none of the 3 batches of Xenid LP® were bioequivalent to Voltaren LP®. Additionally, the batches were not bioequivalent when compared with each other, although the diclofenac pharmacokinetics of batches B and C were similar. The low bioavailability of Xenid LP® compared with the standard sustained-release formulation indicates that the 2 formulations are not therapeutically equivalent and, at a dose level of 100mg, Xenid LP® may actually be ineffective as a maintenance treatment for inflammatory disorders, assuming that the amount of systemically available drug is relevant to the clinical effect.

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Authors and Affiliations

  1. Corning Besselaar Clinical Research Unit, Springfield House, Hyde Street, Leeds, LS2 9NG, England

    I. T. Hooper (Medical Writer), E. Allen, K. McLaughlin & C. Ward

  2. Laboratoires Ciba-Geigy, Rueil-Malmaison, France

    A. Sioufi

Authors
  1. I. T. Hooper
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  2. E. Allen
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  3. K. McLaughlin
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  4. C. Ward
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  5. A. Sioufi
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Hooper, I.T., Allen, E., McLaughlin, K. et al. Bioavailability of a Generic Sustained-Release Formulation of Diclofenac Compared with the Standard Sustained-Release Formulation. Clin. Drug Invest. 12, 259–270 (1996). https://doi.org/10.2165/00044011-199612050-00005

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  • DOI: https://doi.org/10.2165/00044011-199612050-00005

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