Clinical Drug Investigation

, Volume 12, Issue 5, pp 259–270 | Cite as

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

  • I. T. Hooper
  • E. Allen
  • K. McLaughlin
  • C. Ward
  • A. Sioufi


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.


Adis International Limited Drug Invest Voltaren Relative Bioavailability Quantifiable Concentration 
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  1. 1.
    Ku EC, Lee W, Kothari HV, et al. Effect of diclofenac on the arachidonic acid cascade. Am J Med 1986; 80 Suppl. 4B: 18–23PubMedCrossRefGoogle Scholar
  2. 2.
    John VA. The pharmacokinetics and metabolism of diclofenac sodium in animals and in man. In: Haslock I, et al., editors. Diclofenac in the treatment of rheumatic diseases: a conspectus of international experience. Rheumatol Rehabil 1979; 17 Suppl. 2: 22–37Google Scholar
  3. 3.
    Sioufi A, Stierlin H, Schweizer A, et al. Recent findings concerning clinically relevant pharmacokinetics of diclofen sodium. In: Kass E, editor. Voltaren — new findings. Berne, Stuttgart, Vienna: Hans Huber, 1982: 19–30Google Scholar
  4. 4.
    Willis JV, Kendall MJ, Flinn RM, et al. The pharmacokinetics of diclofenac sodium following intravenous and oral administration. Eur J Clin Pharmacol 1979; 16: 405–10PubMedCrossRefGoogle Scholar
  5. 5.
    Voltaren (diclofenac) — twenty years of clinical experience (an update). Basle: Ciba-Geigy Limited, 1994Google Scholar
  6. 6.
    Gibaldi M, Perrier D. Pharmacokinetics: drugs and the pharmaceutical sciences. 2nd rev. ed. 1982: 15Google Scholar
  7. 7.
    Raz I, Hussein Z, Samara E, et al. Comparative pharmacokinetic analysis of a novel sustained-release dosage form of diclofenac sodium in healthy subjects. Int J Clin Pharm Ther Toxicol 1988; 26(5): 246–8Google Scholar
  8. 8.
    Suleiman MS, Najib N, El-Sayed Y, et al. A study on the relative bioavailability of a sustained-release formulation of diclofenac sodium. Int J Clin Pharm Ther Toxicol 1989; 27(6): 276–79Google Scholar
  9. 9.
    Snedocor GW, Cochran WG. Statistical methods. 8th ed. Iowa State Univ Press, 1982: 217–53Google Scholar
  10. 10.
    Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharm Biopharm 1987; 15: 657–80Google Scholar
  11. 11.
    Lehmann EL. Nonparametrics: statistical methods based on ranks. New York: McGraw-Hill, 1975. Chapters 3 and 4Google Scholar
  12. 12.
    Hasan MM, Najib NM, Muti H. A comparative bioavailability study on two sustained-release formulations of diclofenac sodium following a single dose administration. Int J Clin Pharm Ther Toxicol 1993; 31(8): 387–91Google Scholar
  13. 13.
    Sørensen K. A long-term investigation of a new antirheumatic drug, diclofenac sodium (Voltaren). Scand J Rheumatol 1978; Suppl. 22: 81–5Google Scholar
  14. 14.
    Nelson S, Brahim J. An evaluation of the analgesic efficacy of diclofenac potassium, aspirin, and placebo in postoperative dental pain. Todays Ther Trends 1995; 12 Suppl. 1: 3–14Google Scholar

Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • I. T. Hooper
    • 1
  • E. Allen
    • 1
  • K. McLaughlin
    • 1
  • C. Ward
    • 1
  • A. Sioufi
    • 2
  1. 1.Corning Besselaar Clinical Research UnitLeedsEngland
  2. 2.Laboratoires Ciba-GeigyRueil-MalmaisonFrance

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