DOI QR코드

DOI QR Code

Bioequivalence Assessment of Nabumetone Tablets in Healthy Korean Volunteers

  • Park, Moon-Hee (Department of Pharmacology, College of Medicine, Hanyang University) ;
  • Shin, In-Chul (Department of Pharmacology, College of Medicine, Hanyang University)
  • 발행 : 2007.06.30

초록

This study was performed to evaluate the bioequivalency between the Osmetone$^{TM}$ Tablet (Myeongmoon Pharm. Co., Ltd.) as a test formulation and the Relafen$^{TM}$ Tablet (Handok Pharm. Co., Ltd.) as a reference formulation. Twenty-four healthy male volunteers were administered the formulations by the randomized Latin square crossover design, and the plasma samples were determined by a high performance liquid chromatography (HPLC) with Ultra-Violet (UV) detector. AUC$_t$, C$_{max}$ and T$_{max}$ were obtained from the time-plasma concentration curves, and log-transformed AUC$_t$ and C$_{max}$ and log-untransformed T$_{max}$ values for two formulations were compared by statistical tests and analysis of variation. AUC$_t$ was determined to be 897.8${\pm}$431.1 ug.hr/ml for the reference formulation and 902.3${\pm}$408.4 ug.hr/ml for the test formulation. The mean values of C$_{max}$ for the reference and test formulations were 24.2${\pm}$8.9 and 24.0${\pm}$9.5 ug/ml, respectively. The AUC$_t$ and C$_{max}$ ratios of the reference Relafen$^{TM}$ Tablet to the test Osmetone$^{TM}$ Tablet were +5.01% and -0.83%, respectively, showing that the mean differences were satisfied the acceptance criteria within 20%. The results from analysis of variance for logtransformed AUC$_t$ and C$_{max}$ indicated that sequence effects between groups were not exerted and 90% confidence limits of the mean differences for AUC$_t$ and C$_{max}$ were located in ranges from log 0.80 to log 1.25, satisfying the acceptance criteria of the KFDA bioequivalence. The Osmetone$^{TM}$ Tablet as the test formulation was considered to be bioequivalant to the Relafen$^{TM}$ Tablet used as its reference formulation, based on AUC$_t$ and C$_{max}$ values.

키워드

참고문헌

  1. de Jar, A. D., Hundt, H. K., Hundt, A. F., Swart, K. J., Knight, M. and Roberts, J. (2000). Extractionless determination of 6-methoxy-2-naphthylacetic acid, a major metabolite of nabumetone, in human plasma by high performance liquid chromatography. J. Chromatogr. B Biomed. Sci. Appl. 14;740(2), 247-251 https://doi.org/10.1016/S0378-4347(00)00074-8
  2. Friedel, H. A., Langtry, H. D. and Buckley, M. M. (1993). Nabumetone. A reappraisal of its pharmacology and therapeutic use in rheumatic diseases. Drugs 45, 131-156 https://doi.org/10.2165/00003495-199345010-00009
  3. Kobylinska, K., Barlinska, M. and Kobylinska, M. (2003). Analysis of nabumetone in human plasma by HPLC. Application to single dose pharmacokinetic studies. J. Pharm. Biomed. Anal. 1;32(2), 323-328 https://doi.org/10.1016/S0731-7085(03)00078-5
  4. Lee, Y. J., Kim, Y. G., Lee, M. G., Chung, S. J., Lee, M. H. and Shim, C. K. (2000) Analysis of bioequivalence study using log-transformed model. Yakhakhoji 44, 308-314
  5. Mikami, E., Goto, T., Ohno, T., Matsumoto, H. and Nishida, M. (2000). Simultaneous analysis of naproxen, nabumetone and its major metabolite 6-methoxy-2-naphthylacetic acid in pharmaceuticals and human urine by high performance liquid chromatography. J. Pharm. Biomed. Anal. 23(5), 917-925 https://doi.org/10.1016/S0731-7085(00)00365-4
  6. Nobilis, M., Holcapek, M., Kolarova, L., Kopecky, J., Kunes, M., Svoboda, Z. and Kvetina, J. (2004). Identification and determination of phase II nabumetone metabolites by high performance liquid chromatography with photodiode array and mass spectrometric detection. J. Chromatogr. A. 26;1031, 229-236
  7. Nobilis, M., Kopecky, J., Kvetina, J., Svoboda, Z., Pour, M., Kunes, J., Holcapek, M. and Kolarova, L. (2003). Comparative biotransformation and disposition studies of nabumetone in humans and minipigs using high performance liquid chromatography with ultraviolet, fluorescence and mass spectrometric detection. J. Pharm. Biomed. Anal. 8;32, 641-656
  8. Patrignani, P., Panara, M. R., Greco, A., Fusco, O., Natoli, C., Lacobelli, S., Cipollone, F., Ganci, A., Creminon, C., and Maclouf, J. (1994). Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J. Pharmacol. Exp. Ther. 271, 1705-1712
  9. Qin, Y., Zou, Y., Liang, M., Huang, Y. and Yu, Q. (1999). Determination of 6-methoxy-2-naphthylacetic acid, a major metabolite of nabumetone, in human plasma by HPLC. Hua Xi Yi Ke DA Xue Xue Bao 30, 452-454
  10. Ray, J. E. and Day, R. O. (1984). High performance liquid chromatographic determination of a new anti-inflammatory agent, nabumetone and its major metabolite in plasma using fluorimetric detection. J. Chromatogr. 7; 336, 234-238
  11. Schuirmann, D., J. (1987). A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average b ioavailability. J. Pharmacokinet. Biopharm. 15, 657-680 https://doi.org/10.1007/BF01068419
  12. Scott, D. L. and Palmer, R., H. (2000). Safety and efficacy of nabumetone in osteoporosis: emphasis on gastrointestinal safety. Aliment. Pharmacol. Ther. 14, 443-452 https://doi.org/10.1046/j.1365-2036.2000.00715.x
  13. Shargel, L., and Yu, A., B., C. (1993). Chapter 10. Bioavailability and bioequivalence. In: Applied Biopharmaceutics and Pharmacokinetics, 3rd Ed., p.193, Appleton & Lange, Norwalk, USA
  14. Korea Food and Drug Administration (KFDA; Nov 22, 2002a). Standard protocol for the criteria of bioequivalence test, KFDA Notification NO. 2002-60
  15. Korea Food and Drug Administration (KFDA; Nov 22, 2002b). Standard protocol for rgulations of bioequivalence test, KFDA Notification NO. 2002-61