Clinical study on the bioequivalence of two tablet formulations of flurbiprofen
Tóm tắt
Flurbiprofen (CAS 5104-49-4) is a member of phenylaikanoic acid derivative group of nonsteroid anti-inflammatory drugs. It exhibits anti-inflammatory, analgesic and antipyretic activities. Two different tablets containing flurbiprofen (FLU) were investipted in 24 healthy volunteers to prove the bioequivalence between both treatments after single oral dose administrations. Fluroben® 100 mg tablet and 100 mg tablet of the originator product were used as test and reference preparation respectively. The study was performed open label, randomized, two period cross-over design with 15 days wash out period. Blood samples were taken up to 24 hours for pharmacokinetic profiling. The plasma concentrations of flurbiprofen were determined with validated HPLC-UV method. Maximum plasma concentration (Cmax) of FLU 19 143.65 ng/ml and 19 164.22 ng/ml were found for test and reference formulation respectively. Areas under the plasma concentration time curve AUC0-∞ of 118 501.4 ng.h/ml and lii 339.8 ng.h/ml were calculated test and reference formulation respectively. Primary target parameters AUC0-∞ and Cmax, both of them were tested parametrically by analysis of variance (ANOVA); 90% confidence intervals were between 100.5%–111.18% for AUC0-∞ and 87.6%–115.0% for Cmax. All these values were within the acceptance range (80%–125%) for bioequivalence studies.
Tài liệu tham khảo
Roberts L.C., Morrow J.D. (2001). Analgesic-Antipiretic and Antiinflammatory Agents and Drugs employed in the treatment of Gout. In: (Hardman JG, Limbird LE., eds) Goodman&Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. McGraw Hill, mt. Ed., pp.687–731.
Benvenuti C., Gambaro V., Lodi F., Scaroni C., Bandi G., Valenti M. (1989). Single-dose pharmacokinetics of flurbiprofen granules and tablets in healthy volunteers. mt. J. Clin. Pharnacol. Ther. Toxicol., 27, 334–337.
Jamali F., Collins D.S., Berry B.W., Molder S., Cheung R., McColl K., Cheung H. (1991). Comparative bioavailability of two flurbiprofen products: stereospesific versus conventional approach. Biophanm Drug Dispos., 13, 383–387.
Townsend K.P., Praticô D. (2005). Novel therapeutic opportunities for Alzheimer’s disease: focus on nonsteroidal antiinflammatory drugs. Faseb. J., 19, 192–601.
Hassan Y., Alfadly SO., Azmin M.N., Peh K.K., Tan TF.Y., Noorizan A.A., Ismail 0. (2007). Bioequivalence evaluation of two different formulations of ciprofloxacin tablets in healthy volunteers. Singapore Med. J., 48, 819–823.
Hutzler J.M., Frye R.F., Tracy T.S. (2000). Sensitive and spesific high-performance liquid chromatographic assay for 4′-hydroxyflurbiprofen and flurbiprofen in human urine and plazma. J. Chomatogr. B. Biomed. Sci. Appl., 749(1), 119–125.
Giagoudakis G., Markantonis S.L. (1998). An alternative high-performance liquid-chromatografic method for determination if diclofenac and flurbiprofen in plasma. J. Pharmaceutic. Biomed. Analysis., 17, 897–901.
Guidance for Industry, Bioanalytical Method Validation, FDA, May, 2001
Jamali F., Collins D.S., Berry B.W., Molder S., et. al.(1991). Comparative bioavailability of two flurbirofen products: Stereospesific versus conventinal approach. Biopharm. Drug Disp., 12, 435–445.