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Arzneimittelforschung 2009; 59(1): 42-48
DOI: 10.1055/s-0031-1296363
Antimycotics · Antiparasitics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

In vitro Dissolution and in vivo Bioequivalence Evaluation of Two Brands of Cefuroxime Axetil Tablets

Yoonho Choi
1   Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, (South Korea)
,
Su-Eon Jin
1   Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, (South Korea)
,
Mi-Kyung Lee
2   Department of Pharmaceutical Engineering, Woosuk University, Samrye, (South Korea)
,
Chong-Kook Kim
1   Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, (South Korea)
› Author Affiliations
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Publication History

Publication Date:
14 December 2011 (online)

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Abstract

The bioequivalence of two brands of 250 mg cefuroxime axetil (CAS 64544-07-6) tablets was evaluated by in vitro dissolution tests and in vivo bioequivalence tests. The in vitro dissolution test was performed by the paddle method following the guidance of the Korea Food and Drug Administration (KFDA). The in vivo bioequivalence study was designed to be a single dose, randomized, double-blind trial with a 1-week washout period between the doses in 26 healthy volunteers. The results of the dissolution test showed comparable and rapidly dissolving profiles of the two cefuroxime axetil tablets, which were pharmaceutically equivalent. The in vivo study was conducted to evaluate the bioequivalence of the two drug products in humans. In the in vivo bioequivalence study, the plasma samples drawn from the volunteers were analyzed utilizing a sensitive HPLC analysis method with ultraviolet detection. The evaluation of bioequivalence between test and reference products was accomplished by statistical analysis of the log transformed mean ratios of Cmax, AUC0–t and AUC0–8. The mean maximum concentration (Cmax) of the test and the reference were found to be 8.5 ± 2.0 µg/mL and 8.6 ± 2.1 µg/mL, respectively. The 90% C. I. of Cmax was 0.95 to 1.03. As for the AUC0–t and the AUC0–8, test values were 22.6 ± 5.7 µg mL−1 h, 23.5 ± 6.3 µg mL−1 h and the reference values were 25.6 ± 6.6 µg mL−1 h, 26.7 ± 6.8 µg mL−1 h, respectively. The 90% C. I. of AUC0–t was 0.83 to 0.94 and AUC0–8, 0.82 to 0.94. Consequently, all the results fulfilled the standard criteria of bioequivalence, being within the 0.80 to 1.25% range. In addition to the 90% C. I. of the parameters, a two-way ANOVA showed that there was no significant difference between the two products. Based on these statistical analyses, it is concluded that the test product is bioequivalent to the reference product.

Key words

Antibiotics - CAS 64544-07-6 - Cefuroxime axetil, bioequiva-lence, dissolution, HPLC - Cefutil® - Cephalosporins
 

  • References

  • 1 Neu HC, Fu KP. Cefuroxime, a beta-lactamase-resistant cephalosporin with a broad spectrum of gram-positive and -negative activity.. Antimicob Agents Chemother 1978; Apr 13 (4) 657-64
    PubMedGoogle Scholar
  • 2 Brogden RN, Heel RC, Speight TM, Avery GS. Cefuroxime: a review of its antibacterial activity, pharmacological properties and therapeutic use.. Drugs 1979; Apr 17 (4) 233-66
    CrossrefPubMedGoogle Scholar
  • 3 Harding SM, Williams PE, Ayrton J. Pharmacology of Cefuroxime as the 1-acetoxyethyl ester in volunteers.. Antimicrob Agents Chemother 1984; Jan 25 (1) 78-82
    CrossrefPubMedGoogle Scholar
  • 4 AMA Council on Drugs. AMA Drug Evaluations. 6th ed. Chicago: American Medical Association; 1985
    Google Scholar
  • 5 Finn A, Straughn A, Meyer M, Chubb J. Effect of dose and food on the bioavailability of cefuroxime axetil. Biopharm Drug Dispos. 1987; Nov–Dec; 8 (6) 519-26
    CrossrefPubMedGoogle Scholar
  • 6 Williams PE, Harding SM. The absolute bioavailability of oral cefuroxime axetil in male and female volunteers after fasting and after food.. J Antimicrob Chemother 1984; Feb 13 (2) 191-6
    CrossrefPubMedGoogle Scholar
  • 7 Kees F, Lukassek U, Naber KG, Grobecker H. Comparative investigations on the bioavailability of cefuroxime axetil.. Arzneimittelforschung 1991; Aug 41 (8) 843-6
    PubMedGoogle Scholar
  • 8 Sommers DK, van Wyk M, Moncrieff J, Schoeman HS. Influence of food and reduced gastric acidity on the bioavailability of bacampicillin and cefuroxime axetil.. Br J Clin Pharmacol 1984; Oct 18 (4) 535-9
    CrossrefPubMedGoogle Scholar
  • 9 Rojanasthien N, Boonchaliew C, Kumsorn B, Sangdee C. A bioequivalence study of the cefuroxime axetil in healthy volunteers. J Med Assoc Thailand (Chotmaihet thangphaet) 2003; Nov 86 (11) 1063-1072
    PubMedGoogle Scholar
  • 10 Pistos C, Michalea S, Kalovidouris M, Kontopoulos G, Georgarakis M. Bioequivalence evaluation of 2 brands of cefuroxime axetil 250 mg tablets in healthy human volunteers.. Int J Clin Pharmacol Ther 2004; Jul 42 (7) 367-72
    PubMedGoogle Scholar
  • 11 World Health Organization. Multisource (Generic) Pharmaceutical Products: Guidelines on Registration Requirements to Establish Interchangeability 2005
    PubMedGoogle Scholar
  • 12 The United States Pharmacopeia The National Formulary. 29th ed. Rockville: United States Pharmacopeia Convention, Inc.; 2006
    Google Scholar
  • 13 Zivanovic L, Ivanovic I, Vladimirov S, Zecevic M. Investigation of chromatographic conditions for the separation of cefuroxime axetil and its geometric isomer. J Chromatog. 2004; Feb 5 800 (1–2) 175-9
    CrossrefPubMedGoogle Scholar
  • 14 Tuerk J, Reinders M, Dreyer D, Kiffmeyer TK, Schmidt KG, Kuss HM. Analysis of antibiotics in urine and wipe samples from environmental and biological monitoring: comparison of HPLC with UV-, single MS- and tandem MS-detection. J Chromatog. 2006; Feb 2 831 (l–2) 72-80
    CrossrefPubMedGoogle Scholar
  • 15 Korea Food and Drug Administration. KFDA Guideline for Bioequivalence Test 2002
    PubMedGoogle Scholar