Pharmacokinetic - pharmacodynamic model and ampicillin residue depletion after intramammary administration in cows

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Introduction: The objective of this study was to describe a pharmacokinetic–pharmacodynamic (PK/PD) approach for determination of a rational dosage of ampicillin (AMP) and depletion of the antibiotic residues in milk after intramammary administration to cows.

Material and Methods: The cows came from different farms from the Lublin Province area. They (n = 9) received 5 g of the drug, containing 75 mg of AMP sodium in physiological solution, through a syringe tube by intramammary administration. Following single intramammary administration, the milk samples (5 mL) were collected after 2, 4, 6, 8, 10, 24, 36, 48, and 60 h. The liquid chromatography-mass spectrometry analysis was performed on the Agilent 1200 system connected to an AB Sciex API 4000™ mass spectrometer. The pharmacokinetic analysis of the concentrations of the antibiotic in milk was performed using software Phoenix® WinNonlin® 6.4. Calculations were made in non-compartmental (slopes, highest, amounts, and moments) and compartmental analysis.

Results: The pharmacokinetic characteristics of AMP after intramammary administration indicate rapid elimination of the drug from milk. The mean residence time had a several-fold lower value than the designated elimination half-life and amounts to only 3.4 h. The concentration of the drug in the milk dropped relatively quickly and the process was very dynamic.

Conclusion: The conducted research confirms the rationale of using the PK/PD model in order to verify the dosing regimen for other antibiotic groups and various indicators of the applied PK/PD model.

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  • 1. Berghash S.R. Davidson J.N. Armstrong J.C. Dunny G.M.: Effects of antibiotic treatment of nonlactating dairy cows on antibiotic resistance patterns of bovine mastitis pathogens. Antimicrob Agents Chemother 1983 5 771–776.

  • 2. Burmańczuk A. Roliński Z. Kowalski C. Zań R.: Concentration of cefacetril in milk after its intramammary administration to cows with health and inflamed mammary gland. Bull Vet Inst Pulawy 2011 55 685–688.

  • 3. Cervinkova D. Vlkova H. Borodacova I. Makovcova J. Babak V. Lorencova A. Vrtkova I. Marosevic D. Jaglic Z.: Prevalence of mastitis pathogens in milk from clinically healthy cows. Med Weter 2013 58 567–575.

  • 4. Christensen J.M. Smith B.B. Murdena S.B. Hollingshead N.: The disposition of five therapeutically important antimicrobial agents in llamas. J Vet Pharmacol Ther 1996 19 43–438.

  • 5. Concordet D. Toutain P.L.: The withdrawal time estimation of veterinary drugs revisited. J Vet Pharmacol Ther 1997 20 380–386.

  • 6. Craigmill A.L. Pass M.A. Wetzlich S.: Comparative pharmacokinetics of AMX administered intravenously to sheep and goats. J Vet Pharmacol Ther 1992 15 72–77.

  • 7. Delis G.A. Koutsoviti-Papadopoulou M. Siarkou V.I. Kounenis G. Batzias G.C.: Pharmacodynamics of amoxicillin against Mannheimia haemolytica and Pasteurella multocida and pharmacokinetic/pharmacodynamic (PK/PD) correlation in sheep. Res Vet Sci 2010 89 418–425.

  • 8. Elsheikh H.A. Taha A. Khalafalla A. Osman I. Wasfi I.: Pharmacokinetics of amoxicillin trihydrate in Desert sheep and Nubian goats. Vet Res Commun 1999 23 507–514.

  • 9. Escudero E. Espuny A. Vicente M.S. Cárceles C.M.: Comparative pharmacokinetics of an ampicillin/sulbactam combination administered intramuscularly in lactating sheep and goats. Can J Vet Res 1999 1 25–30.

  • 10. Escudero E. Cárceles C.M. Vicente S.: Pharmacokinetics of amoxicillin/clavulanic acid combination and of both drugs alone after intravenous administration to goats. Vet J 1998 152 551–559.

  • 11. EMEA. Penicillins Summary Report. Committee for Veterinary Medicinal Products 2008 1–2.

  • 12. Fernandez C. Modamio P. Mestorino N. Errecalde J.O. Marino E.L.: Pharmacokinetics of sodium and trihydrate amoxycillin in sheep after intravenous and intramuscular administration. J Vet Pharmacol Ther 2007 30 263–266.

  • 13. Fernandez-Varon E. Escudero-Pastor E. Carceles-Rodriguez C.: Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to neonatal calves. Vet J 2005 169 437–443.

  • 14. Frimodt-Moller.: How predictive PK/PD for antibacterial agents. Int J Antimicrob Ag 2002 4 333–339.

  • 15. Garg S.K. Chaudhary R.K. Srivastava A.K.: Disposition kinetics and dosage of cephalexin in cow calves following intramuscular administration. Ann Rech Vet 1992 23 399–402.

  • 16. Gehring R. Van der Merve D. Pierce A.N Baynes R.E. Craigmill A.L. Riviere J.E.: Multivariate meta-analysis of pharmacokinetic studies of ampicilin trihydrate in cattle. Am J Vet Res 2005 66 108–112.

  • 17. Gibaldi M. Perrier D.: Pharmacokinetics. Marcel Dekker New York 1982.

  • 18. Grunt P. Maincent P. Berthelot X. Kaltsatos V.: Bovine mastitis and intramammary drug delivery; review and perspectives. Adv Drug Deliv Rev 2001 50 245–259.

  • 19. Guerrini V.H. Filippich L.J Cao G.R. English P.B. Bourne D.W.: Pharmacokinetics of cefaronide ceftriaxone and cefoperazone in sheep. J Vet Pharmacol Ther 1985 8 120–127.

  • 20. Guterbock W.W Eenennaam A.L Anderson R.J. Gardner I.A. Cullor J.S. Homberg C.A.: Efficacy of intramammary antibiotic therapy for treatment of clinical mastitis caused by environmental pathogens. J Dairy Sci 1993 76 3437–3441.

  • 21. Jacoby G.A. Munoz-Price L.S.: The new beta-lactamases. New Engl J Med 2005 352 380–391.

  • 22. Jayachandran C. Singh M.K. Banerjee N.C.: Pharmacokinetics and distribution of ampicillin in plasma milk and uterine fluid of female buffaloes. Vet Res Commun 1990 14 47–51.

  • 23. Kreil V.E. Ambrosa L. Montoyaa L. Hallua R. Rebueltoa M. Bramuglia G.: Pharmacokinetics of sodium and trihydrate amoxicillin after intravenous and intramuscular administration in llamas (Lama glama). Small Ruminant Res 2012 102 208–212.

  • 24. Kreil V. Lüders C. Hallu R. Rebuelto M. Betancourt L.: Pharmacokinetics of ampicillin in Alpacas (Lama pacos). Arch Med Vet 2001 2 241–246.

  • 25. Li Y. Wang L. Gu x. Zeng Z. He L. Yang F. Yuan B. Shu J. Ding H.: Pharmacokinetics and residues of cefquinome in milk of lactating Chinese dairy cows after intramammary administration. J Integr Agr 2014 13 2750–2757.

  • 26. McKeller Q.A. Sanchez Bruni S.F. Jones D.G.: Pharmacokinetic/pharmacodynamic relationships of antimicrobial drug used in veterinary medicine. J Vet Pharmacol Ther 2004 27 503–514.

  • 27. Movassagh M.H. Karami A.R.: Beta-lactam antibiotics residues in pasteurised milk by Beta Star test in the north-west region of Iran. ARPN J Agri Biol Sci 2011 6 7–10.

  • 28. Prades M. Brown M.P. Gronwall R. Miles N.S.: Pharmacokinetics of sodium cephapirin in lactating dairy cows. Am J Vet Res 1988 49 1888–1894.

  • 29. Rajala-Schultz P.J. Smith K.L. Hogan J.S. Love B.C.: Antimicrobial susceptibility of mastitis pathogens from first lactation and older cows. Vet Microbiol 2004 102 33–42.

  • 30. Toutain P.L. del Castillo J.R. Bousquet-Melou A.: The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics. Res Vet Sci Oct 2002 73 105–114.

  • 31. VET 01-S2: Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals. Sec Inform Suppl 2013 33 25-29.

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