Systemic and mammary gland disposition of enrofloxacin in healthy sheep following intramammary administration

BMC Veterinary Research

Nélida Fernández¹  Ana Maria Sahagún¹  Claudia Pérez²  María José Diez¹  Matilde Sierra¹  Juan José García¹  Cristina López¹ 

[1] Pharmacology, Department of Biomedical Sciences, Institute of Biomedicine (IBIOMED), University of León, Campus de Vegazana s/n, León, 24071, Spain;Department of Animal Health, University of León, Campus de Vegazana s/n, León, 24071, Spain

关键词: Disposition;    Glandular tissue;    Systemic;    Intramammary;    Sheep;    Enrofloxacin;   

Others  :  1175038
DOI  :  10.1186/s12917-015-0406-9

 received in 2014-12-26, accepted in 2015-03-30,  发布年份 2015

【 摘 要 】

Background

Mastitis is one of the most important diseases affecting dairy sheep. Antimicrobial drugs are often administered directly through teat to treat or prevent this disease, but data on drug distribution within glandular tissue are scarce and it cannot be estimated from concentrations in milk. Thus, the aim of this study was to investigate systemic and mammary gland distribution of enrofloxacin after intramammary administration. The drug was administered to 6 healthy lactating Assaf sheep with an injector containing an enrofloxacin preparation (1 g drug/5 g ointment). Blood samples were collected at 0, 30, 60, 90, 120, 150 and 180 min. Animals were then sedated and sacrificed, and glandular tissue samples were obtained from treated udders at 2, 4, 6 and 8 cm height. Enrofloxacin concentrations were measured in plasma and tissue samples by UV high-performed liquid chromatography.

Results

Mean enrofloxacin plasma concentrations were below 0.5 μg/mL. Mean tissue concentrations decreased in mammary gland with vertical distance from the teat, ranging from 356.6 μg/g at 2 cm to 95.60 μg/g at the base of the udder. Glandular tissue concentrations best fitted to a decreasing monoexponential model, and showed a good correlation with an ex vivo model previously developed.

Conclusions

Enrofloxacin concentrations were effective in the entire glandular tissue against the main pathogens causing mastitis in sheep. These results suggest that this drug may be suitable to treat mastitis in sheep by intramammary administration.

【 授权许可】

   
2015 Lopez et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Bergonier D, Berthelot X: New advances in epizootiology and control of ewe mastitis. Livest Prod Sci 2003, 79:1-16.
• [2]Bergonier D, de Cremoux R, Rupp R, Lagriffoul G, Berthelot X: Mastitis of dairy small ruminants. Vet Res 2003, 34:689-716.
• [3]Contreras A, Sierra D, Sánchez A, Corrales JC, Marco JC, Paape MJ, et al.: Mastitis in small ruminants. Small Rumin Res 2007, 68:145-53.
• [4]Altreuther P: Data on chemistry and toxicology of Baytril®. Vet Med Rev 1987, 2:87-9.
• [5]Elsheikh HA, Taha AAW, Khalafallah AI, Osma IAM: Disposition kinetics of enrofloxacin (Baytril® 5%) in sheep and goats following intravenous and intramuscular injection using a microbiological assay. Res Vet Sci 2002, 73:125-9.
• [6]Scheer M: Studies on the antibacterial activity of Baytril®. Vet Med Rev 1987, 2:90-9.
• [7]Scheer M: Concentrations of active ingredient in the serum and in tissue after oral and parenteral administration of Baytril®. Vet Med Rev 1987, 2:104-18.
• [8]Kaartinen L, Salonen M, Älli L, Pyörälä S: Pharmacokinetics of enrofloxacin after single intravenous, intramuscular and subcutaneus injections in lactating cows. J Vet Pharmacol Ther 1995, 18:357-62.
• [9]Kaartinen L, Pyörälä S, Moilanen M, Raisanen S: Pharmacokinetics of enrofloxacin in newborn and one-week-old calves. J Vet Pharmacol Ther 1997, 20:479-82.
• [10]Bregante MA, Saez P, Aramayona JJ, Fraile L, Garcia MA, Solans C: Comparative pharmacokinetics of enrofloxacin in mice, rats, rabbits, sheep and cows. Am J Vet Res 1999, 60:1111-6.
• [11]Varma R, Ahmad AH, Sharma LD, Aggarwal P, Ahuja V: Pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in cows following single dose intravenous administration. J Vet Pharmacol Ther 2003, 26:303-5.
• [12]Kumar N, Singh SD, Jayachandran C: Pharmacokinetic study of diclofenac and its interaction with enrofloxacin in buffalo calves. J Vet Sci 2003, 2:155-9.
• [13]Sharma PK, Ahmad AH, Sharma LD, Varma R: Pharmacokinetics of enrofloxacin and the rate of formation of its metabolite ciprofloxacin following intravenous and intramuscular single dose administration to male buffalo calves. Vet J 2003, 166:101-4.
• [14]Mengozzi G, Intorre L, Bertini S, Soldani G: Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and intramuscular administration in sheep. Am J Vet Res 1996, 57:1040-3.
• [15]Bermingham EC, Papich MG: Pharmacokinetics after intravenous and oral administration of enrofloxacin in sheep. Am J Vet Res 2002, 63:1012-7.
• [16]Otero JL, Mestorino N, Errecalde JO: Pharmacokinetics of enrofloxacin after single intravenous administration in sheep. Rev Sci Techn 2009, 28:1129-42.
• [17]Elmas M, Tras B, Kaya S, Bas AL, Yazar E, Yarsan E: Pharmacokinetics of enrofloxacin after intravenous and intramuscular administration in Angora goats. Can J Vet Res 2001, 65:64-7.
• [18]Ambros L, Montoya L, Kreil V, Waxman S, Albarellos G, Rebuelto M, et al.: Farmacocinética de la enrofloxacina y su metabolito ciprofloxacina en cabras. Rev Argent Prod Anim 2007, 27(Supl 1):329-30.
• [19]Vancutsem PM, Babish JG, Schwark WS: The fluoroquinolone antimicrobials: structure, antimicrobial activity, pharmacokinetics, clinical use in domestic animals and toxicity. Cornell Vet 1990, 80:173-86.
• [20]López C, Fernández N, Sierra M, Diez MJ, Gonzalo JM, Sahagún AM, et al.: Tissue distribution of enrofloxacin after intramammary and systemic administration in the isolated perfused sheep udder. Am J Vet Res 2012, 73:1728-34.
• [21]Manceau J, Gicquel M, Laurentie M, Sanders P: Simultaneous determination of enrofloxacin and ciprofloxacin in animal biological fluids by high-performance liquid chromatography. Application in pharmacokinetics studies in pig and rabbit. J Chromatogr 1999, 726:175-84.
• [22]Diaz D, Picco EJ, Encinas T, Rubio M, Litterio NJ, Boggio JC: Residuos tisulares de nicotinato de norfloxacina administrado por vía oral en cerdos. Arch Med Vet 2001, 33:37-42.
• [23]Ehinger AM, Kietzmann M: Pharmakokinetische aspekte der mastitistherapie. Berl Munch Tierarztl Wochenschr 1998, 9:337-43.
• [24]Ehinger AM, Kietzmann M: Tissue distribution of oxacillin and ampicillin in the isolated perfused bovine udder. J Vet Med 2000, 47:157-68.
• [25]Ehinger AM, Kietzmann M: Tissue distribution of benzylpenicillin after intramammary administration in the isolated perfused bovine udder. J Vet Pharmacol Ther 2000, 23:303-10.
• [26]Ehinger AM, Schmidt H, Kietzmann M: Tissue distribution of cefquinome after intramamary and systemic administration in the isolated perfused bovine udder. Vet J 2006, 172:147-53.
• [27]Kietzmann M, Niedorf F, Gossellin J: Tissue distribution of cloxacillin after intramammary administration in the isolated perfused bovine udder. BMC Vet Res 2010, 6:46. BioMed Central Full Text
• [28]Funke H: The distribution of 35S-labelled benzylpenicillin in normal and mastitic mammary glands of cows and goats after local and systemic administration. Acta Vet Scand 1961, 2(Suppl 1):11-88.
• [29]Moore GA, Heider LE: Treatment of mastitis. Vet Clin North Am Large Anim Pract 1984, 6:323-33.
• [30]Zeitlin IJ, Eshraghi HR: The release and vascular action of bradykinin in the isolated perfused bovine udder. J Physiol 2002, 543:221-31.
• [31]Goutalier J, Combeau S, Quillon JP, Goby L: Distribution of cephalexin and kanamycin in the mammary tissue following intramammary administration in lactating cow. J Vet Pharmacol Ther 2012, 36:95-8.
• [32]Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Disk and Dilution Susceptibility Test for Bacteria Isolated from Animals. 3rd edition. Clinical and Laboratory Standards Institute, Wayne, PA; 2008.
• [33]De Garnica ML, Rosales RS, Gonzalo C, Santos JA, Nicholas RA: Isolation, molecular characterization and antimicrobial susceptibilities of isolates of Mycoplasma agalactiae from bulk tank milk in an endemic area of Spain. J Appl Microbiol 2013, 114:1575-81.
• [34]Bengtsson B, Ericsson H, Ekman T, Artursson K, Nilsson-Öst M, Persson K: Antimicrobial susceptibility of udder pathogens from cases of acute clinical mastitis in dairy cows. Vet Microbiol 2009, 136:142-9.
• [35]Blondeau JM, Borsos S, Blondeau LD, Blondeau BJ, Hesje CE: Comparative minimum inhibitory and mutant prevention drug concentrations of enrofloxacin, ceftiofur, florfenicol, tilmicosin and tulathromycin against bovine clinical isolates of Mannheimia haemolytica. Vet Microbiol 2012, 160:85-90.
• [36]Feßler A, Scott C, Kadlec K, Ehricht R, Monecke S, Schwarz S: Characterization of methicillin-resistant Staphylococcus aureus ST398 from cases of bovine mastitis. J Antimicrob Chemother 2010, 65:619-25.
• [37]Rubin JE, Ball KR, Chirino-Trejo M: Antimicrobial susceptibility of Staphylococcus aureus and Staphylococcus pseudintermedius isolated from various animals. Can Vet J 2011, 52:153-7.
• [38]Baba K, Ishihara K, Ozawa M, Usui M, Hiki M, Tamura Y, et al.: Prevalence and mechanism of antimicrobial resistance in Staphylococcus isolates from diseased cattle, swine and chickens in Japan. J Vet Med Sci 2012, 74:561-5.
• [39]Kaspar H: Results of the antimicrobial agent susceptibility study raised in a representative, cross-sectional monitoring study on a national basis. Int J Med Microbiol 2006, 296(Suppl 2):69-79.
• [40]McKellar QA, Sanchez SF, Jones DG: Pharmacokinetic/pharmadynamic relationships of antimicrobial drugs used in veterinary medicine. J Vet Pharmacol Ther 2004, 27:503-14.
• [41]Papich MG: Pharmacokinetic-pharmacodynamic (PK-PD) modelling and the rational selection of dosage regimes for the prudent use of antimicrobial drugs. Vet Microbiol 2014, 171:480-6.