Evaluation of allometric scaling as a tool for extrapolation of the enrofloxacin dose in American black vultures (Coragyps atratus)

Samanta Waxman 1Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Chorroarin 280, 1427 Buenos Aires, Argentina.

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Ana P. Prados 1Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Chorroarin 280, 1427 Buenos Aires, Argentina.

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José J. De Lucas 2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290, 1425 Buenos Aires, Argentina.
3Departamento de Farmacología y Toxicología, Facultad de Veterinaria, Universidad Complutense de Madrid, Ciudad Universitaria, s/n. 28040 Madrid, Spain.

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Guillermo Wiemeyer 4Ecoparque, R. de la India 3000, 1425 Buenos Aires, Argentina.
5The Peregrine Fund, 5668 W Flying Hawk Ln, Boise, ID 83709.
6Fundación Caburé-í, Sucre 2842, 1428 Buenos Aires, Argentina.

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Laura Torres-Bianchini 4Ecoparque, R. de la India 3000, 1425 Buenos Aires, Argentina.

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Manuel I. San Andres 2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290, 1425 Buenos Aires, Argentina.
3Departamento de Farmacología y Toxicología, Facultad de Veterinaria, Universidad Complutense de Madrid, Ciudad Universitaria, s/n. 28040 Madrid, Spain.

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Casilda Rodríguez 2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290, 1425 Buenos Aires, Argentina.
3Departamento de Farmacología y Toxicología, Facultad de Veterinaria, Universidad Complutense de Madrid, Ciudad Universitaria, s/n. 28040 Madrid, Spain.
1Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Chorroarin 280, 1427 Buenos Aires, Argentina.
2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290, 1425 Buenos Aires, Argentina.
3Departamento de Farmacología y Toxicología, Facultad de Veterinaria, Universidad Complutense de Madrid, Ciudad Universitaria, s/n. 28040 Madrid, Spain.
4Ecoparque, R. de la India 3000, 1425 Buenos Aires, Argentina.
5The Peregrine Fund, 5668 W Flying Hawk Ln, Boise, ID 83709.
6Fundación Caburé-í, Sucre 2842, 1428 Buenos Aires, Argentina.

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Abstract

OBJECTIVE

To determine the pharmacokinetics of enrofloxacin after IV administration in American black vultures (Coragyps atratus), to compare clearance of enrofloxacin in American black vultures with clearance of this fluoroquinolone in other avian species, and to evaluate whether allometric scaling is an appropriate tool for dose extrapolation in avian species.

ANIMALS

6 healthy adult American black vultures.

PROCEDURES

Enrofloxacin concentrations were quantified by use of high-performance liquid chromatography. Pharmacokinetics of enrofloxacin was determined in American black vultures after IV administration. Pharmacokinetic parameters for 12 avian species obtained from 24 pharmacokinetic studies were used. Allometric analysis of enrofloxacin pharmacokinetic parameters was performed.

RESULTS

Volume of distribution at steady state for enrofloxacin was 3.47 L/kg, clearance was 0.147 L/h·kg, and elimination half-life was 18.3 hours. Comparisons among avian species revealed that American black vultures had the lowest extraction ratio for enrofloxacin (1.04%). Only the volume of distribution at steady state and clearance had a good allometric fit. Goodness of fit was improved when ratites were not included in the analysis.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that the use of allometric scaling for the prediction of volume of distribution at steady state could provide a suitable method for extrapolation of enrofloxacin doses among avian species; however, allometric scaling could not be used to adequately predict the clearance of enrofloxacin.

Abstract

OBJECTIVE

To determine the pharmacokinetics of enrofloxacin after IV administration in American black vultures (Coragyps atratus), to compare clearance of enrofloxacin in American black vultures with clearance of this fluoroquinolone in other avian species, and to evaluate whether allometric scaling is an appropriate tool for dose extrapolation in avian species.

ANIMALS

6 healthy adult American black vultures.

PROCEDURES

Enrofloxacin concentrations were quantified by use of high-performance liquid chromatography. Pharmacokinetics of enrofloxacin was determined in American black vultures after IV administration. Pharmacokinetic parameters for 12 avian species obtained from 24 pharmacokinetic studies were used. Allometric analysis of enrofloxacin pharmacokinetic parameters was performed.

RESULTS

Volume of distribution at steady state for enrofloxacin was 3.47 L/kg, clearance was 0.147 L/h·kg, and elimination half-life was 18.3 hours. Comparisons among avian species revealed that American black vultures had the lowest extraction ratio for enrofloxacin (1.04%). Only the volume of distribution at steady state and clearance had a good allometric fit. Goodness of fit was improved when ratites were not included in the analysis.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that the use of allometric scaling for the prediction of volume of distribution at steady state could provide a suitable method for extrapolation of enrofloxacin doses among avian species; however, allometric scaling could not be used to adequately predict the clearance of enrofloxacin.

Contributor Notes

Dr. Prados's present address is Animal Clinic of Sierra de los Padres, Sierra de los Padres, 7601, Buenos Aires, Argentina.

Dr. Torres-Bianchinni's present address is Ministerio de Salud y Desarrollo Social, Av 9 de Julio, 1925 Buenos Aires, Argentina.

Address correspondence to Dr. Rodríguez (rodfermc@vet.ucm.es).
  • 1. Naidoo V, Duncan N, Bekker L, et al. Validating the domestic fowl as a model to investigate the pathophysiology of diclofenac in Gyps vultures. Environ Toxicol Pharmacol 2007;24:260266.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Naidoo V, Wolter K, Cuthbert R, et al. Veterinary diclofenac threatens Africa's endangered vulture species. Regul Toxicol Pharmacol 2009;53:205208.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Garcia-Montijano M, Waxman S, de Lucas JJ, et al. Disposition of marbofloxacin in vulture (Gyps fulvus) after intravenous administration of a single dose. Res Vet Sci 2011;90:288290.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. International Union for Conservation of Nature. The IUCN red list of threatened species. Available at: www.iucnredlist.org. Accessed Feb 18, 2018.

    • Search Google Scholar
    • Export Citation
  • 5. Wink M. Phylogeny of Old and New World vultures (Aves: Accipitridae and Cathartidae) inferred from nucleotide sequences of the mitochondrial cytochrome b gene. Z Naturforsch C 1995;50:868882.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Dermody BJ, Tanner CJ, Jackson AL. The evolutionary pathway to obligate scavenging in Gyps vultures. PLoS One 2011;6:e24635.

  • 7. Carpenter JW. Pharmacotherapeutics in companion birds: an update and review, in Proceedings. 31st World Small Anim Vet Cong 2006;14.

    • Search Google Scholar
    • Export Citation
  • 8. López-Cadenas C, Sierra-Vega M, Garcia-Vieitez JJ, et al. Enrofloxacin: pharmacokinetics and metabolism in domestic animal species. Curr Drug Metab 2013;14:10421058.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Hawkins MG, Barron HW, Speer BL, et al. Antimicrobial agents used in birds. In: Carpenter JW, ed. Exotic animal formulary. 4th ed. St Louis: Elsevier Saunders, 2013;184216.

    • Search Google Scholar
    • Export Citation
  • 10. Waxman S, Prados AP, de Lucas J, et al. Pharmacokinetic and pharmacodynamic properties of enrofloxacin in southern crested caracaras (Caracara plancus). J Avian Med Surg 2013;27:180186.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Grubb BR. Allometric relations of cardiovascular function in birds. Am J Physiol 1983;245:H567H572.

  • 12. Toutain PL, Bousquet-Mélou A. Plasma clearance. J Vet Pharmacol Ther 2004;27:415425.

  • 13. Haritova A, Urumova V, Lutckanov M, et al. Pharmacokinetic-pharmacodynamic indices of enrofloxacin in Escherichia coli O78/H12 infected chickens. Food Chem Toxicol 2011;49:15301536.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Abd el-Aziz MI, Aziz MA, Soliman FA, et al. Pharmacokinetic evaluation of enrofloxacin in chickens. Br Poult Sci 1997;38:164168.

  • 15. Anadón A, Martínez-Larrañaga MR, Díaz MJ, et al. Pharmacokinetics and residues of enrofloxacin in chickens. Am J Vet Res 1995;56:501506.

    • Search Google Scholar
    • Export Citation
  • 16. Bailey TA, Sheen RS, Silvanose C, et al. Pharmacokinetics of enrofloxacin after intravenous, intramuscular and oral administration in houbara bustard (Chlamydotis undulata macqueenii). J Vet Pharmacol Ther 1998;21:288297.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Bugyei K, Black WD, McEwen S. Pharmacokinetics of enrofloxacin given by the oral, intravenous and intramuscular routes in broiler chickens. Can J Vet Res 1999;63:193200.

    • Search Google Scholar
    • Export Citation
  • 18. de Lucas JJ, Rodriguez C, Waxman S, et al. Pharmacokinetics of enrofloxacin after single intravenous and intramuscular administration in young domestic ostrich (Struthio camelus). J Vet Pharmacol Ther 2004;27:119122.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. de Lucas JJ, Rodríguez C, Martella MB, et al. Pharmacokinetics of enrofloxacin following intravenous administration to greater rheas: a preliminary study. Res Vet Sci 2005;78:265267.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Dimitrova DJ, Lashev LD, Yanev SG, et al. Pharmacokinetics of enrofloxacin in turkeys. Res Vet Sci 2007;82:392397.

  • 21. García Ovando H, Gorla N, Luders C, et al. Comparative pharmacokinetics of enrofloxacin and ciprofloxacin in chickens. J Vet Pharmacol Ther 1999;22:209212.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Haritova A, Djeneva H, Lashev L, et al. Pharmacokinetics and PK/PD modelling of enrofloxacin in Meleagris gallopavo and Gallus domesticus. Bulg J Vet Med 2004;7:139148.

    • Search Google Scholar
    • Export Citation
  • 23. Haritova A, Dimitrova D, Dinev T, et al. Comparative pharmacokinetics of enrofloxacin, danofloxacin, and marbofloxacin after intravenous and oral administration in Japanese quail (Coturnix japonica). J Avian Med Surg 2013;27:2331.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Harrestien LA, Tell LA, Vulliet R, et al. Disposition of enrofloxacin in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus) after a single oral, intramuscular or intravenous dose. J Avian Med Surg 2000;14:228236.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Helmick KE, Boothe DM, Jensen JM. Disposition of single-dose intravenously administered enrofloxacin in emus (Dromaius novaehollandiae). J Zoo Wildl Med 1997;28:4348.

    • Search Google Scholar
    • Export Citation
  • 26. Knoll U, Glünder G, Kietzmann K. Comparative study of the plasma pharmacokinetics and tissue concentrations of danofloxacin and enrofloxacin in broiler chickens. J Vet Pharmacol Ther 1999;22:239246.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Lashev LD, Dimitrova DJ, Milanova A, et al. Pharmacokinetics of enrofloxacin and marbofloxacin in Japanese quails and common pheasants. Br Poult Sci 2015;56:255261.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Soliman GA. Tissue distribution and disposition kinetics of enrofloxacin in healthy and E. coli infected broilers. Dtsch Tierarztl Wochenschr 2000;107:2327.

    • Search Google Scholar
    • Export Citation
  • 29. Tansakul N, Poapolathep A, Klangkaew N, et al. Pharmacokinetics and withdrawal times of enrofloxacin in ducks. Kasetsart J Nat Sci 2005;39:235239.

    • Search Google Scholar
    • Export Citation
  • 30. Wack AN, KuKanich B, Bronson E, et al. Pharmacokinetics of enrofloxacin after single dose oral and intravenous administration in the African penguin (Spheniscus demersus). J Zoo Wildl Med 2012;43:309316.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Baert K, De Backer P. Comparative pharmacokinetics of three non-steroidal anti-inflammatory drugs in five bird species. Comp Biochem Physiol C Toxicol Pharmacol 2003;134:2533.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Clark AJ. The influence of body weight on the size of the heart in warm-blooded animals. In: Clark AJ, ed. Comparative physiology of the heart. Cambridge, England: Cambridge University Press, 2015;7186.

    • Search Google Scholar
    • Export Citation
  • 33. Hunter RP. Interspecies allometric scaling. In: Cunningham FE, Lees P, eds. Comparative and veterinary pharmacology. New York: Springer-Verlag Berlin Heidelberg, 2010;140157.

    • Search Google Scholar
    • Export Citation
  • 34. Buckley NJ. Black vulture: Coragyps atratus. Birds of North America. Available at: birdsna.org/Species-Account/bna/species/blkvul/introduction. Accessed Feb 18, 2018.

    • Search Google Scholar
    • Export Citation
  • 35. Bregante MA, Saez P, Aramayona JJ, et al. Comparative pharmacokinetics of enrofloxacin in mice, rats, rabbits, sheep, and cows. Am J Vet Res 1999;60:11111116.

    • Search Google Scholar
    • Export Citation
  • 36. Cox SK, Cottrell MB, Smith L, et al. Allometric analysis of ciprofloxacin and enrofloxacin pharmacokinetics across species. J Vet Pharmacol Ther 2004;27:139146.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Mahmood I. Application of allometric principles for the prediction of pharmacokinetics in human and veterinary drug development. Adv Drug Deliv Rev 2007;59:11771192.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38. Haritova AM, Lashev LD. Comparison of the pharmacokinetics of seven fluoroquinolones in mammalian and bird species using allometric analysis. Bulg J Vet Med 2009;12:324.

    • Search Google Scholar
    • Export Citation
  • 39. Mukaka MM. Statistics corner: a guide to appropriate use of correlation coefficient in medical research. Malawi Med J 2012;24:6971.

    • Search Google Scholar
    • Export Citation
  • 40. de Lucas JJ, Rodríguez C, Waxman S, et al. Pharmacokinetics of marbofloxacin after intravenous and intramuscular administration to ostriches. Vet J 2005;170:364368.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41. Naidoo V, Wolter K, Cuthbert R, et al. Veterinary diclofenac threatens Africa's endangered vulture species. Regul Toxicol Pharmacol 2009;53:205208.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42. Olofsson SK, Marcusson LL, Komp Lindgren P. Selection of ciprofloxacin resistance in Escherichia coli in an in vitro kinetic model: relation between drug exposure and mutant prevention concentration. J Antimicrob Chemother 2006;57:11161121.

    • Crossref
    • Search Google Scholar
    • Export Citation

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