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Bioequivalence study of nabumetone tablets in man

Abstract

A nabumetone tablet in development (NabutonR) was tested for its bioequivalence to the reference tablet (UnitonR). Seventeen healthy Korean male subjects participated in this study. Each subject received a 1-g dose of nabumetone (2 tablets each) in an unbalanced, randomized, two-way crossover investigation. Serum concentrations of 6-methoxy-2-naphthylacetic acid (6-MNA), a major metabolite of nabumetone, were measured over 120 hr interval by a high-performance liquid chromatography. The maximum serum concentration (Cmax) and time to reach the maximum concentration (Tmax) were read directly, but area under the serum concentration time curve from time 0 to 120 hr (AUC) and mean residence time (MRT) of 6-MNA were calculated from the serum 6-MNA concentration-time curves. The serum curves showed multiple peaks of 6-MNA in most subjects, and the Cmax and Tmax were read from the highest serum peaks. Calculated bioavailability parameters for test and reference tablets were 1498.6∶1377.9 μg·hr/ml for AUC; 25.2∶23.1 μg/ml for Cmax; 11.8∶16.4 hr for Tmax and 42.6∶43.8 hr for MRT, respectively. The pairedt-test revealed no significant differences in all the parameters between the two tablets. Analysis of variance (ANOVA) revealed no significant differences between groups and formulations in all the parameters (Cmax, Tmax, AUC and MRT) indicating the crossover design of the experiment was properly performed. But significant differences (p<0.05) between subject/groups and periods were found for all the parameters indicating substantial intersubject and interperiodic variations for these parameters.

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References Cited

  1. Concise Statistical Tables, Japan Association of Standardization. 1976, pp 50–51.

  2. Daigneault, E. A., Ferslew, K. E. and Stanton, P., Bioequivalence study of nabumetone: tablet versus suspension.Am. J. Medicine, 83, 11–14 (1987).

  3. Food and Drug Administration (FDA). Division of Biopharmaceutics.Bioavailability Protocol Guideline for ANDA and NDA Submission, 1977.

  4. Food and Drug Administration (FDA). Report by the bioequivalence task force on recommendation from the bioequivalence hearing conducted by the FDA, 29, September, 1986-1, Octerber, 1988.

  5. Friedel, H. A. and Todd, P. A., Nabumetone—a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in rheumatic disease.Drugs, 35, 504–524, 1988.

  6. Haddock, R. E., Teffery, D. J., Lloyd, J. A. and Thawley, A. R., Metabolism of nabumetone (BRL 14777) by various species including man.Xenobiotica 14, 327–337, 1984.

  7. Jang, E. J., Lee, Y. J., Park, M. G. S. and Shim, C. K., HPLC assay of 6-methoxy-2-naphthylacetic acid, a major metabolite of nabumetone, in human serum.Anal. Lett. 28, 2379–2389, 1995.

  8. Korean Guidelines for Bioequivalence Test. National Institute of Safety Research, Korea, 1988.

  9. Mangan, F. R., Flack, J. D., and Jackson, D., Preclinical overview of nabumetone pharmacology, bioavailability, metabolism, and toxicology.Am. J. Medicine, 83, 6–10, 1987.

  10. Ogata, H. and Ejima, A.,Bioavailability and Bioequivalence Test of Drugs, Yakugyo Jiho Co., Ltd., Tokyo, Japan, 1989, pp. 70–72.

  11. Schuirmann, D. J., Use of logarithmic transformation for analysis of bioavailability/bioequivalence data. Paper presented at the DIA-Workshop on Bioavailability/Bioequivalence: Pharmacokinetic and Statistical Considerations, Bethesda, Md., August 5–7, 1991, Audio Transcripts Ltd. Alexandria, 1991.

  12. Shim, C. K., Report on bioequivalence test of NabutonR tablet. Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1994.

  13. Shim, C. K. and Hong, J. S., Inter- and intrasubject variations of ranitidine pharmacokinetics after oral administration to normal male subjects.J. Pharm. Sci., 78, 990–994, 1989.

  14. Shim, C. K. and Jung, B. H., Inter- and intrasubject variations of multiple saliva peaks of acetaminophen after oral administration of tablets.Int. J. Pharm., 82, 233–237, 1992a.

  15. Shim, C. K. and Jung, B. H., Noncontribution of enterohepatic recycling to multiple plasma peaks of acetaminophen after oral administration to rats.Int. J. Pharm., 83, 257–262, 1992b.

  16. Shim, C. K. and Suh, M. K., Multiple plasma peaks of acetaminophen and ranitidine after simultaneous oral administration to rats.Arch. Pharm. Res., 15, 246–250, 1992.

  17. Steinijans, V. W., Hauschke, D. and Jonkman, J. H. G., Controversies in bioequivalence studies.Clin. Pharmacokin., 22, 247–253, 1992.

  18. Tsuchiya, K. Statistical analysis for bioequivalence studies. InHuman Studies for Healthy Subjects, Tsunoo, M. (Ed.), Seishi Shoin, 1985, pp. 210–225.

  19. Von, Schrader, H. W., Buscher, G., Dierdorf, D., Mugge, H. and Wolf, D., Nabumetone—a novel anti-inflammatory drug: the influence of food, milk, antacids, and analgesics on bioavailability of single oral doses.Int. J. Clin. Pharmacol. Therap. Toxicol, 21, 311–321, 1983.

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Correspondence to Chang-Koo Shim.

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Lee, Y., Jang, E., Lee, J. et al. Bioequivalence study of nabumetone tablets in man. Arch. Pharm. Res. 18, 340–345 (1995). https://doi.org/10.1007/BF02976329

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Key words

  • Nabumetone
  • 6-Methoxy-2-naphthylacetic acid (6-MNA)
  • Bioquivalence
  • AUC
  • Cmax, Tmax, MRT
  • Multiple peaks
  • ANOVA