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2011, Number 3

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Vet Mex 2011; 42 (3)

Bioequivalence of two amoxicillin-potassium clavulanate oral preparations in dogs

Hayashida S, Gutiérrez L, Luna VJ, Osnaya F, Sumano H

Language: English/Spanish
References: 28
Page: 197-205
PDF size: 155.14 Kb.


ABSTRACT

The aim of this trial was to carry out a bioequivalence (BE) study in dogs using a generic preparation of amoxicillin-potassium clavulanate vs a commercially available reference preparation, both claiming to achieve plasma concentrations that allow a 12 h dosing interval after oral administration. The oral pharmacokinetic profiles of a single dose of each preparation were carried out in 12 adult mongrel dogs in a crossover model with a 10 day washout period at a dose of 12.5 mg/kg of trihydrate amoxicillin and potassium clavulanate as tablets. A composite determination of amoxicillin-potassium clavulanate concentration in each sample of plasma was carried out in triplicate, using a microbiological agar diffusion analysis. Pharmacokinetic analysis was carried out with a non-compartmental model. Statistical analysis of pharmacokinetic variables was carried out by ANOVA and Bonferroni t test, setting a P ‹ 0.05. In accordance with international standards, it was found that the generic preparation failed to be bioequivalent, i.e: AUC0-∞ 9.08 ± 0.26 μg h/ml and Cmax 5.48 ± 0.19 μg/ml for the generic preparation vs AUC0-∞ 13.28 ± 0. 30 μg h/ml and Cmax 2.9 ± 0.17 μg/ml for the reference one. A 0.25 μg/ml breakpoint can be set as minimum effective plasma concentration for amoxicillin; hence the generic preparation requires a dose interval of eight h.


REFERENCES

  1. FRANCIS ME, MARSHALL AB, TURNER WT. Amoxicillin: clinical trials in dogs and cats. Vet Rec 1978; 102: 377-380.

  2. RICHMOND MH, SYKES RB. The ß-lactamases of gram-negative bacteria and their possible physiologic role. In: ROSE AH, TEMPEST DW, editors. Advances in Microbial physiology. Vol 9. London: Academic Press, 1973: 31-38.

  3. BROWN AG, BUTTERWORTH D, COLE M, HANSCOMB G, HOOD JD, READING C et al. Naturally- occurring ß lactamase inhibitors with antibacterial activity. J Antibiot 1976; 29: 668-669.

  4. READING C, COLE M. Clavulanic acid: A ß-lactamaseinhibiting ß-lactam from Streptomyces clavuligerus. Antimicrob Agents Chemother 1977; 11: 852-857.

  5. KAYE CM, ALLEN A, PERRY S, MCDONAGH M, DAVY M, STORM K et al. The Clinical Pharmacokinetics of a new pharmacokinetically enhaced formulation of amoxicillin/ clavulanate. Clin Ther 2001; 23: 578-584.

  6. BYWATER RJ, PALMER GH, BUSWELL JF, STANTON A. Clavulanate- potentiated amoxicillin: Activity in vitro and bioavailability in the dog. Vet Rec 1985; 116: 33-36.

  7. VREE TB, DAMMERS E, VAN DUURE E. Variable absorption of clavulanic acid after an oral dose of 25 mg/kg of Clavubactin™ and Synulox™ in healthy dogs. J Vet Pharmacol Ther 2003; 26: 165-171.

  8. KERC J, OPARA J. A new amoxicillin/clavulanate therapeutic system: Preparation, in vitro and pharmacokinetic evaluation. Int J Pharm 2007; 335: 106-113.

  9. BARR WH, ZOLA EM, CANDLER EL, HWANG SM, TENDOLKAR AV, SHAMBUREK R et al. Differential absorption of amoxicillin from the human small and large intestine. Clin Pharmacol Ther 1994; 56: 279-285.

  10. OGATA H, AOYAGI N. Bioavailability of nalidixic acid from uncoated tablets in humans and in vitro dissolution rates. Int J Clin Pharmacol Toxicol Ther 1984; 22: 240-245.

  11. LUI CY, AMIDON GM, BERARDI RR, FLEISHER D, YOUNGBERG C. Comparison of gastrointestinal pH in dogs and humans: implications on the use of the beagle dogs as a model for oral absorption in humans. J Pharm Sci 1986; 75: 271-274.

  12. BENNETT JV, BRODIE JL, BRENNER EJ, KIRBY J. Simplified accurate method for antibiotic assay of clinical specimens. Appl Microbiol 1966; 14: 170 – 177.

  13. EUROPEAN MEDICINES AGENCY. Committee for veterinary medicinal products: Guidelines for the Conduct of Bioequivalence studies for Veterinary Medicinal Products. London: EMA, 2001.

  14. RIVIERE JE. Unique problems associated with the determination of veterinary drug preparation bioequivalence. J Vet Pharmacol Ther 1994; 17: 86-88.

  15. STEINIJANS V, HAUSCHKE D, JONKMAN G. Controversies in bioequivalence studies. Clin Pharmacokinet 1992; 22: 247-253.

  16. CRAIG WA. Pharmacokinetic/Pharmacodynamic parameters: Rationale for Antibacterial Dosing of mice and men. Clin Infect Dis 1998; 26:1-12.

  17. ARANCIBIA A, GUTTMANN J, GONZALEZ G, GONZALEZ C. Absorption and disposition kinetics of amoxicillin in normal human subjects. Antimicrob Agents Chemother 1980; 17: 199–202.

  18. MARIER JF, BEAUDRY F, DUCHARME MP, FORTIN D, MOREAU JP, MASSÉ R et al. A pharmacokinetic study of amoxicillin in febrile beagle dogs following repeated administrations of endotoxin. J Vet Pharmacol Ther 2001; 24: 379-383.

  19. ZIA H, SHALCHIAN N, BORHANIAN F. Kinetics of amoxicillin degradation in aqueous solution. Can J Pharmacol Sci 1977; 12:80-83.

  20. WESTPHAL JF, DESLANDES A, BROGARD JM, CARBON C. Reappraisal of amoxicillin absorption kinetics. J Antimicrob Chemother 1991; 27:647-654.

  21. LI M, ANDERSON GD, PHILLIPS BR, KONG W, SHEN DD, WANG J. Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos 2006; 34: 547-555.

  22. WEITSCHIES W, FRIEDRICH C, WEDEMEYER RS, SCHMIDTMANN M, KOSCH O, KINZIG M et al. Bioavailability of amoxicillin and clavulanic acid from extended release tablets depends on intragastric tablet deposition and gastric emptying. Eur J Pharm Biopharm 2008; 2:641-648.

  23. CLINICAL AND LABORATORY STANDARDS INSTITUTE. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals. Approved Standard. 2nd ed. Wayne PA: NCCLS document M31-A, 2004.

  24. GANIERE JP, MEDAILLE C, MANGION C. Antimicrobial Drug susceptibility of Staphylococcus intermedius Clinical Isolates from canine Pyoderma. J Vet Med 2005; 52: 25-31.

  25. PAPICH MC. Susceptibility testing in animals- How breakpoints are derived and interpretation of susceptibility data. Proceeding of 15th AAVPT Biennial Symposium; 2007 May 20-24; Pacific Grove, California. [Serial online: 2007 May] [Cited: 2010 December 13]. Available from: http://www.ivis.org/proceedings/aavpt/2007/papich.pdf

  26. ROY J, MESSIER S, LABRECQUE O, COX WR. Clinical and in vitro efficacy of amoxicillin against bacteria associated with feline skin wounds and abscesses. Can Vet J 2007; 48: 607-611.

  27. GOODMAN LS, GILMAN A. The Pharmacological basis of Therapeutics. 2nd ed. New York: Macmillan, 1956.

  28. AMBROSE PGJ, OWENS RC, GRASELA D. Antimicrobial pharmacodynamics. Med Clin North Am 2000; 84: 1431-1446.




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