Open-label, randomized, crossover comparative bioavailability study of cefixime from two tablet formulations after single oral administration
Keywords:Cefixime, Bactericidal, Bioequivalence, High-performance liquid chromatographic
Background: Cefixime is an oral extended spectrum third generation cephalosporin, which has marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram-negative organisms, effective in the treatment of community-acquired infections such as respiratory tract infection and urinary tract infection. The objective of this randomized, crossover study was to compare the bioequivalence (BE) of two tablets of test (Milixim® 200 mg, containing 200 mg of cefixime) with Reference formulation (Cefixime, 400 mg).
Methods: A total of 12 healthy volunteers were randomly assigned to crossover, single-dose treatment regimens. Serial blood samples were collected, and plasma concentrations of cefixime were analyzed using the high-performance liquid chromatographic technique. Pharmacokinetic parameters and BE limits were calculated using non-compartmental methods.
Results: The mean Cmax for the test and reference formulations were 4435.0298±149 and 4408.2150±1021 ng/mL, respectively. The mean area under the serum concentration curve (AUC)0-t were 38108.2614±8583.6535 and 38457.5791±8105.2529 ng/hr/mL The mean ratios (test: reference) for Cmax, AUC0-t, were 99.7% and 98.5%, respectively. There were no significant differences in pharmacokinetic parameters between groups. Overall, the 90% confidence interval for the intra-individual ratios of the log-transformed Cmax and AUC values of the two formulations were within the BE interval of 80-125%.
Conclusion: The study has demonstrated the BE of milixim and reference formulation of cefixime.
Understanding generic drugs. US Food and Drug Administration, Silver Spring; 2012. Available at http://www.fda.gov/Drugs/ResourcesForYou/Consumers/Buying UsingMedicineSafely/UnderstandingGeneric Drugs/default.htm. Accessed 05 Apr 2013.
Kanfe r I, Shargel L. Generic Drug Product Development, International Regulatory Requirements for Bioequivalence. New York: Informa Healthcare; 2010: 1-16.
Brogden RN, Campoli-Richards DM. Cefixime. A review of its antibacterial activity. Pharmacokinetic properties and therapeutic potential. Drugs. 1989;38(4):524-50.
Stone JW, Linong G, Andrews JM, Wise R. Cefixime, in-vitro activity, pharmacokinetics and tissue penetration. J Antimicrob Chemother. 1989;23(2):221-8.
Wu DH. Efficacy and tolerability of cefixime in otitis media. A multicentre study in over 25,000 children. Drugs. 1991;42 Suppl 4:30-2.
Dreshaj Sh, Doda-Ejupi T, Tolaj IQ, Mustafa A, Kabashi S, Shala N, et al. Clinical role of Cefixime in community-acquired infections. Prilozi. 2011;32(2):143-55.
Faulkner RD, Sia LL, Barone JS, Forbes SJ, Silber BM. Bioequivalency of oral suspension formulations of cefixime. Biopharm Drug Dispos. 1989;10(2):205-11.
Zakeri-Milani P, Valizadeh H, Islambulchilar Z. Comparative bioavailability study of two cefixime formulations administered orally in healthy male volunteers. Arzneimittelforschung. 2008;58(2):97-100.
Asiri YA, Al-Said MS, Al-Khamis KI, Niazy EM, El-Sayed YM, Al-Rashood KA, et al. Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers. Int J Clin Pharmacol Ther. 2005;43(10):499-504.
Guideline, the Investigation of Bioequivalence. Committee for Medicinal Products for Human Use (CHMP), European Medicines Agency (EMA); 2010. Available at http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf. Accessed 05 Apr 2013.
Faulkner RD, Bohaychuk W, Desjardins RE, Look ZM, Haynes JD, Weiss AI, et al. Pharmacokinetics of cefixime after once-a-day and twice-a-day dosing to steady state. J Clin Pharmacol. 1987;27(10):807-12.
Schall R, Luus HG. Comparison of absorption rates in bioequivalence studies of immediate release drug formulations. Int J Clin Pharmacol Ther Toxicol. 1992;30(5):153-9.
Guidance for Industry, Bioavailability and Bioequivalence Studies for Orally Administered drug Products; General Considerations. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER); July, 2002 BP.