Bioequivalence Study of Two Formulations Containing 400 mg Dexibuprofen in Healthy Indian Subjects
15 December 2011 (online)
This study presents the results of two-period, two-treatment crossover investigations on 24 healthy Indian male subjects to assess the bioequivalence of two oral formulations containing 400 mg of dexibuprofen (CAS 51146–56–6). An attempt was also made to study the pharmacokinetics of dexibuprofen in the local population of Indian origin.
Both of the formulations were administered orally as a single dose separated by a one-week washout period. The concentration of dexibuprofen in plasma was determined by a validated HPLC method with UV detection using carbamazepine as internal standard. The formulations were compared using the parameters area under the plasma concentration-time curve (AUC0–t), area under the plasma concentration-time curve from zero to infinity (AUC0–∞), peak plasma concentration (Cmax), and time to reach peak plasma concentration (tmax).
The results of this investigation indicated that there were no statistically significant differences between the logarithmically transformed AUC0–∞ and Cmax values of the two preparations. The 90% confidence interval for the ratio of the logarithmically transformed AUC0–t, AUC0–∞ and Cmax were within the bioequivalence limit of 0.8–1.25 and the relative bioavailability of the test formulation was 99.04% of that of reference formulation.
Thus, these findings clearly indicate that the two formulations are bioequivalent in terms of rate and extent of drug absorption. Both preparations were well tolerated with no adverse reactions observed throughout the study.
- 1 Busson M. Update on ibuprofen: review article. J Int Med Res. 1986; 14: 53-62
- 2 Mehlisch DR, Jasper RD, Brown P, Korn SH, McCarroll K, Murakami AA. Comparative study of ibuprofen lysine and acetaminophen in patients with postoperative dental pain. Clin Ther. 1995; 17: 852-860
- 3 Bonenberg E, Zou MH, Ullrich V. Inhibition of cyclooxyge-1 and -2 by R (-) and S(+) -ibuprofen. J Clin Pharmacol. 1996; 36: 16S-19S
- 4 Brideau C, Kargman S, Liu S, Dallob AL, Ehrich EW, Rodger IW et al. A human whole blood assay for clinical evaluation of biochemical efficacy of cyclo-oxygenase inhibitors. Inflamm Res. 1996; 45: 68-72
- 5 Young JM, Panah S, Satchawatcharaphong C, Cheung PS. Human whole blood assays for inhibition of prostaglandin G/H synthases-1 and - 2 using A23187 and lipopolysac-charide stimulation of thromboxane B2 production. In-flamm Res. 1996; 45: 246-253
- 6 Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Anna Rev Pharmacol Toxicol. 1998; 38: 97-120
- 7 Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR. No steroid drug selectivities for cyclooxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sei USA. 1999; 96: 7563-7568
- 8 Wechter JW, Loughhaed DG, Reischer RJ, VanGiessen GJ, Kaiser DG. Enzymatic inversion at saturated carbon: nature and mechanism of the inversion of R (−) p-iso-butyl hydro-tropic acid. Biochem Biophys Res Commun. 1974; 61: 833-837
- 9 Caldwell J, Hutt AJ, Fournel-Gigleux S. The metabolic chiral inversion and dispositional enantioselectivity of the 2-aryl-propionic acids and their biological consequences. Biochem Pharmacol. 1988; 37: 105-114
- 10 Williams KM. Enantiomers in arthritic disorders. Pharmacol Ther. 1990; 46: 273-295
- 11 Greennan DM, Aarons L, Siddiqui M, Richards M, Thompson R, Higham C. Dose- response study with ibuprofen in rheumatoid arthritis: clinical and pharmacokinetic findings. Br J Clin Pharmacol. 1983; 15: 311-316
- 12 Laska EM, Sunshine A, Marrero I, Olson N, Siegel C, Mc-Cormick N. The correlation between blood levels of ibuprofen and clinical analgesic response. Clin Pharmacol Ther. 1986; 40: 1-7
- 13 Bonabello A, Galmozzi MR, Canaparo R, Isaia GC, Serpe L, Muntoni E et al. Dexibuprofen (S (+)-isomer ibuprofen] reduces gastric damage and improves analgesic and antiinflammatory effects in rodents. Anesth Analg. 2003; 97: 402-408
- 14 Dionne RA, McCullagh L. Enhanced analgesia and suppression of plasma ß-endorphin by the S (+)-isomerof ibuprofen. Clin Pharmacol Ther. 1998; 63: 694-701
- 15 Mehvar R, Jamall F, Pasutto FM. Liquid-chromatographic assay of ibuprofen enantiomers in plasma. Clin Chem. 1988; 34 (3) 493-496
- 16 Vinci F, Fabbrocino S, Fiori M, Serpe L. Gallo R Determination of fourteen non- steroidal anti-inflammatory drugs in animal serum and plasma by liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom. 2006; 20: 3412-3420
- 17 Wang P, Qi M, Liu L, Fang L. Determination of ibuprofen in dog plasma by liquid chromatography and application in pharmacokinetic studies of an ibuprofen prodrug in dogs. Journal of Pharmaceutical and Biomedical Analysis. 2005; 38: 714-719
- 18 Hauschke D, Steinijans V, Diletti E. A distribution free procedure for the statistical analysis of bioequivalence studies. Int J Clin Pharmacol Ther Toxicol. 1990; 30: 37-43
- 19 Schulz HU, Steinijans VW. Striving for standards in bioequivalence assessment: a review. Int J Clin Pharmacol Ther Toxicol. 1992; 30: 51-56
- 20 Farolfi M, Power JD, Rescigno A. On the determination of bioequivalence. Pharmacol. Res. 1999; 39: 1-4
- 21 Mandal U, Musmade P, Chakraborty M, Rajan DS, Chakravarti M, Pal TK et al. Bioequivalence study of sildenafil citrate tablets in healthy human volunteers. Boll Chim Farmac. 2004; 143: 345-349
- 22 Mandal U, Ganesan M, Pal TK, Jayakumar M, Chattaraj TK, Ray K et al. Bioequivalence study of rabeprazole sodium on healthy human volunteers. J Indian Med Assoc. 2004; 102 (1) 26-30
- 23 Mandal U, Jayakumar M, Ganesan M, Senthil DR, Pal TK, Gowda VK. Bioequivalence study on quetiapine fumarate tablets by HPLC. Indian Drugs. 2005; 42 (6) 353-356
- 24 Gowda KV, Rajan DS, Mandai U, Selvan PS, Solomon WDS, Bose A et al. Evaluation of bioequivalence of two formulations containing 100 miligrams of aceclofenac. Drug Development and Industrial Pharmacy. 2006; 32: 1219-1225
- 25 EMEA. Note for guidance on the investigation of bioavailability and bioequivalence. 2002;CPMP/EWP/QWP/1401/98.
- 26 U. S. Food and Drug Administration. Guidance for Industry: Bioavailability and Bioequivalence studies for orally Administered Drug Products- General Considerations. Rockville, MD: Center for Drug Evaluation and Research. 2000.
- 27 Committee for Proprietary Medicinal Products (CPMP). Note for Guidance: Investigation of Bioavailability and Bioequivalence. London: Working Party on the Efficacy of the Medicinal Products. 1991.
- 28 Nation RL, Sansom LN. Bioequivalence requirements for generic products. Pharmacol. Ther. 1994; 62: 41-55
- 29 Shah VP, Midha KK, Sighe S. Analytical method validation: bioavailability, bioequivalence and pharmacokinetic studies. Eur J Drug Metab Phatrmacokin. 1992; 16: 249-255
- 30 Belen S, Miguel A, Campanero Maria JMJ, Isabel GA, Emilio GQ et al. A comparative study of the pharmacokinetics of ibuprofen arginate versus dexibuprofen in healthy volunteers. Eur J Clin Pharmacol. 2006; 62: 849-854