DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20184328

Disposition kinetics, in vitro plasma protein binding and tissue residues of tilmicosin in healthy and experimentally (CRD) infected broiler chickens

Taha Attia, Amera Abd El Latif, Saber El-Hanbally, Hanem El-Gendy

Abstract


Background: Several studies assayed the pharmacokinetics of tilmicosin in broilers at a dosage of (25mg/kg.b.wt.). The aim of this study was to investigate the pharmacokinetics and tissue residues of tilmicosin following single and repeated oral administrations (25mg/kg.b.wt.) once daily for 5 consecutive days in healthy and experimentally Mycoplasma gallisepticum and E. coli infected broilers.

Methods: After oral administrations of tilmicosin (25 mg/kg.b.wt.) one ml blood was collected from the right wing vein and tissues samples for determination of tilmicosin concentrations and the disposition kinetics of it by the microbiological assay method using Bacillus subtilis (ATCC 6633) as a test organism.

Results: In this study, the plasma concentration time graph was characteristic of a two-compartments open model. Following a single oral administration, tilmicosin was rapidly absorbed in both healthy and experimentally infected broilers with an absorption half-life of (t0.5(ab)) 0.45 and 0.52h, maximum serum concentration (Cmax) was 1.06 and 0.69μg/ml at (tmax) about 2.56 and 2.81h, (t0.5(el)) was 21.86 and 22.91h and (MRT) was 32.15 and 33.71h, respectively; indicating the slow elimination of tilmicosin in chickens. The in-vitro protein binding was 9.72±0.83%. Serum concentrations of tilmicosin following repeated oral administration once daily for five consecutive days, almost peaked 2h after each dose with lower significant values recorded in experimentally infected broiler chickens than in healthy ones.

Conclusions: This study showed that tilmicosin was cleared rapidly from tissues. The highest residue values were recorded in the lung followed by liver and kidneys while the lowest values were recorded in spleen, fat and thigh muscles. Five days for withdrawal period of tilmicosin suggested in broilers.


Keywords


Bioavailability, Broiler Chicken, E. coli, Kinetic, Mycoplasma, Tissue residues, Tilmicosin

Full Text:

PDF

References


Mattoes HM, Nightingale CH. Pharmacokinetics/pharmacodynamics of macrolides. InMacrolide Antibiotics 2002:25-36. Birkhäuser, Basel.

Jelić D, Antolović R. From erythromycin to azithromycin and new potential ribosome-binding antimicrobials. J Antibiotics. 2016;5(29):1-13.

Prescott JF. Lincosamides, macrolides, and pleuromutilins.In: Antimicrobial therapy in veterinary medicine, eds. Prescott JF, Baggot JD, Walker RD, 3rd Ed., Iowa State University Press, Ames, USA, IA.; 2000:229-262.

Charleston B, Gate JJ, Aitken IA, Reeve-Johnson. Assessment of the efficacy of tilmicosin as a treatment for Mycoplasma gallisepticum infections in chickens. Avian Pathology. 1998;27(2):190-5.

Warren MJ, Peters AR, Brett TR, Stocker J. Lung and air sac concentrations of tilmicosin following oral administration in chicken. J Vet Pharmacol Therap. 1997;20:195-6.

Scorneaux B, Shryock TR. Intracellular accumulation, subcellular distribution, and efflux of tilmicosin in chicken phagocytes. Poult Sci. 1998;77(10):1510-21.

Elsayed M, Elkomy A, Aboubakr M, Morad M. Tissue Residues, Hematological and Biochemical Effects of Tilmicosin in Broiler Chicken. Vet Med Int. 2014;502872.

Belah, Soad S, El- Gebaly, Lobna S, Zoghbi, Galal AF, et al. Influence of tilmicosin on some hematological, biochemical and immunological parameters in broilers experimentally infected with mycoplasma. Egypt J Agric Res. 2012;90(1):17-26.

Khairy N, Ammar AM, Eissa SI, Yousreya H. Molecular studies on M. gallisepticum and avian pathogenic E. coli induced infection in broilers. Zag Vet J. 2012;40(6):130-44.

Arret B, Johnson DP, Kirshboum A. Outline of details for microbiological assay of antibiotics: second revision. J Pharma Sci. 1971;60(11):1689-94.

Yamaoka K, Nakagawa T, Uno T. Statistical moment in pharmacokinetics. J Pharmaco Biopharmace. 1978;6:547-58.

Baggot JD. Some aspects of clinical pharmacokinetics in veterinary medicine. J Vet Pharmacol Therape. 1978;1:5-18.

Snedecor GW, Cochran T. Statistical Methods; 6th Ed. Ames, lowa U.S.A., 1976;502-503.

Abu-Basha EA, Idkaidek M, Al-Shunnaq A. Pharmacokinetics of Tilmicosin (Provitil Powder and Pulmotil Liquid AC) Oral Formulations in Chickens. Vet Res Communica. 2007;31(4):477-85.

Keles O, Bakirel T, Sener S. Pharmacokinetics and tissue levels of tilmicosin in fowls. Tur J Vete Ani Sci. 2001;25:629-34.

Kowalski C, Roliński Z, Zań R, Wawron W. Pharmacokinetics of tylosin in broiler chickens. Pol J. Vet Sci. 2002;5(3):127-30.

Li JC. Studies on Stability of Tilmicosin Solution and Pharmacokinetics of Tilmicosin in Broiler Chicken. Master's thesis, China Agricultural University, Basic Veterinary Science; 2003.

McKay SG, Morck DW, Merrill JK, Olson ME, Chan SC, Pap KM. Use of tilmicosin for treatment of pasteurellosis in rabbits. Ame J Vet Resea. 1996;57(8):1180-4.

Abu-Basha EA, Al-Shunnaq AF, Ronette G. Comparative pharmacokinetics and bioavailability of two tylosin formulations in chickens after oral administration. J Hellenic Vet Med Soc. 2012;63(2):159-66.

El-Ela FI, El-Banna HA, El-Deen MB, El-Gendy AA, Tohamy MA. Pharmacokinetics of Tylvalosin alone or in combination with Vitamin E in broiler chickens.

Abo-El-Sooud K, Fahmy E, Afifi A, El-Aty A. Pharmacokinetics and bioavailability of azithromycin following intramuscular and oral administrations in broiler chickens. Res Rev Bio Sci. 2012;6:264-70.

El-Komy A, Abd El-Hakim A, El Sayed M, Gamal El-Din A, Mobarez EA, Azoz HA, et al. Pharmacokinetics Of Tilmicosin In Healthy And Experimentally Pastreulla Multocida Infected Lactating Goats. World J Pha Pharmac Sci. 2016;5(6):2429-38.

Shu G, Li Y, Xiong H. The Study on Pharmacokinetics of Tilmicosin at a Single Oral Dose in Chickens. (Sichuan Agricultural University, Ya'an, Sichuan 625014, China). China Poultry; 2004.

Abeer MR. Pharmacokinetics and Bioavailability of Tylvalosin after oral, intramuscular and intravenous administration in Turkeys. Int J Pharm Pharm Sci. 2016;8(2):140-4.

Cerda RO, Petruccelli M, Piscopo M, Origlia, Landoni M. Impact of the type of catheter on the absorption of tylvalosin (acetylvaleryltylosin) administered orally to broiler chickens. J Vet Pharmacol Ther. 2010;33:202-3.

Shen J, Li C, Jiang H, Zhang S, Guo P, Ding S, Li X. Pharmacokinetics of tilmicosin after oral administration in swine. Ame J Vet Rese. 2005;66(6):1071-4.

Tulay A, Muammer E. Milk and Blood Pharmacokinetics of Tylosin and Tilmicosin following Parenteral Administrations to Cows. Hindawi Publishing Corporation Sci Wor J. Volume 2014, Article ID 869096, 6 pages.

Goudah A, Abo El Sooud K, Abd El-Aty AM. Pharmacokinetics and tissue residue profiles of erythromycin in broiler chickens after different routes of administration. Dtsch. Tierarztl Wochenschr. 2004;111(4):162-5.

Kowalski C, Pomorska-Mól1 M. Evaluation of the bioequivalence of two erythromycin thiocyanate formulations after oral administration to broiler Chickens. Bull Vet Inst Pulawy. 2009;53:247-50.

Cerda RO, Petruccelli M, Piscopo M, Origlia, Landoni M. Impact of the type of catheter on the absorption of tylvalosin (acetylvaleryltylosin) administered orally to broiler chickens. J Vet Pharmacol Ther. 2010;33:202-3.

Haddad NS, Pedersol JP, Ravis WR, Fazel MH, Carson RL. Pharmacokinetics of gentamicin at steady-state in ponies, serum, urine and endometrial concentration. Am J Vet Res. 1985;46(6):1268-71.

Zakeri-Milani P, Ghanbarzadeh S, Poor FL, Milani M, Valizadeh H. Pharmacokinetic study of two macrolide antibiotic oral suspensions using an optimized bioassay procedure. J Bioequivalence Bioavailability. 2010;2:111-5.

Atef, M, Abo el-Sooud K, Nahed E, Tawfik M. Elimination of tilmicosin in lactating ewes. Dtsch Tierarztl Wochenschr. 1999;106(7):291-4.

Baggot JD. Distribution of antimicrobial agents in normal and diseased animals. J Am Vet Med Assoc. 1980;176:1085-90.

Modric S, Webb AI, Davidson M. Effect of respiratory tract disease on pharmacokinetics of tilmicosin in rats. Lab Anim Sci. 1999;49(3):248-53.

Prats C, Francesch R, Arboix M, P´erez B. Determination of tylosin residues in different animal tissues by high performance liquid chromatography. J Chromato B. 2002;766(1):57-65.

Zhang Y, Jiang H, Jin X, Shen Z, Shen J, Fu C, Guo J. Residue depletion of tilmicosin in chicken tissues. J Agric Food Chem. 2004;52(9):2602-5.

Amro FH, Hassan MA, Mahmoud AH. Spiramycin Residues in Chicken Meat And Giblets. Benha Vet Med J. 2013;24(1):51-61.

Soliman AM, Sedeik M. Pharmacokinetics and tissue residues of tylosin in broiler chickens. Pharmacol Pharma. 2016 Jan 13;7(01):36.