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

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.

Tilmicosin Pharmacokinetics and Tissue Residues in Healthy and Naturally Respiratory Infected Broilers

“…Regarding of tilmicosin pharmacokinetic after single intracrop administration, the drug was firstly detected at 0.25 h after administration, peaked at 2h post-administration, and decreased gradually till reaching the lowest drug concentration achieved at 24 hr post drug administration. The result of Cmax (1.49 µg/ml), reported in the present study was found to be closely connected to that testified by Attia et al(2018) for tilmicosin in broilers (1.06 µg/ml) and for tilmicosin in rabbits (1.31µg/ml) at 12.5 mg/kg but lower than that stated by Abu-Basha et al(2007) for tilmicosin (Pulmotil AC ® ) in broilers (2.12 μg/ml) at 30 mg/kg, and that reported by Gallina et al,(2010). This discrepancy could be attributed to dose, species differences, and/or the drug assaying process.In contrast, time to peak plasma level (tmax 3.01) was longer compared to that determined by McKay et al (1996) for tilmicosin in rabbits (2h), Abu-Basha et al (2007) for tylosin in chicken (2.36 h), Attia et al (2018) and Shaban et al (2019) for tilmicosin in broilers (2.56h and 2.1h, respectively) but lower than that estimated by Abu-Basha et al (2007) in broilers for tilmicosin (Pulmotil AC ® ) (5.82h) at 30 mg/kg.…”

“…The result of Cmax (1.49 µg/ml), reported in the present study was found to be closely connected to that testified by Attia et al(2018) for tilmicosin in broilers (1.06 µg/ml) and for tilmicosin in rabbits (1.31µg/ml) at 12.5 mg/kg but lower than that stated by Abu-Basha et al(2007) for tilmicosin (Pulmotil AC ® ) in broilers (2.12 μg/ml) at 30 mg/kg, and that reported by Gallina et al,(2010). This discrepancy could be attributed to dose, species differences, and/or the drug assaying process.In contrast, time to peak plasma level (tmax 3.01) was longer compared to that determined by McKay et al (1996) for tilmicosin in rabbits (2h), Abu-Basha et al (2007) for tylosin in chicken (2.36 h), Attia et al (2018) and Shaban et al (2019) for tilmicosin in broilers (2.56h and 2.1h, respectively) but lower than that estimated by Abu-Basha et al (2007) in broilers for tilmicosin (Pulmotil AC ® ) (5.82h) at 30 mg/kg. The cause of these differences could be attributed to species and dose variation, medication administration routes, and the presence of food in the chicken crop, which would alter crop motions, as well as the consistency of the feed, which could affect crop emptying.…”

“…Following single intracrop administrations of the current investigation, plasma tilmicosin levels in NRI broilers were significantly lower than those in healthy ones. These lower concentrations in infected broilers were consistent with the result formerly stated for tilmicosin by Attia et al (2018) and might be due to the drug's increased penetrating capacity into diseased tissues (Baggot, 1980).Tilmicosin has good tissue penetration and reaches a high concentration and mount up in the lungs of rats than plasma and infection/inflammation further improve its tissue penetration (Modric et al, 1999). This is reliable with the rapid elimination of the drug in diseased birds indicated by the shorter elimination halflife in diseased birds (t½el 8.89h) as compared with the value for healthy ones (t½el 11.32h).…”

“…The cause of these differences could be attributed to species and dose variation, medication administration routes, and the presence of food in the chicken crop, which would alter crop motions, as well as the consistency of the feed, which could affect crop emptying. Furthermore, the presence of lactobacillus flora in the crop, which may be responsible for macrolide inactivation (Cerda et al, 2010).Tilmicosin was rapidly absorbed, with a short absorption half-life (t0.5ab, 0.59 h), similar to what Abo- El-Sooud et al (2012) found for azithromycin in broiler chickens (t0.5ab 0.57h), Attia et al, (2018) for tilmicosin in broiler chickens (0.52 hr) but shorter than those stated by Li (2003) for tilmicosin in broilers (0.948h and 0.757h) and that reported by Shu et al (2004) for tilmicosin in chicken (0.66h) which could be due to individual differences (Cerda et al, 2010). Tilmicosin has been gradually eliminated with elimination half-life (t0.5el 11.32 h).This result is closely connected to that reported by Shaban et al (2019) for tilmicosin in broilers (13.49 hours), but lower than those recorded for tilmicosin in chicken (30.18, 24.18, 47.4, and 21.86 hours) as determined by Keles et al (2001); Li (2003); Abu-Basha et al, (2007); Attia et al, (2018), respectively.…”

Pharmacokinetics of Tildipirosin in Healthy and Mycoplasma gallisepticum Infected Chickens

“…These findings were in concordance with those of Salman et al (2016) who reported that the serum concentrations of tylvalosin was significantly lower in M. gallisepticum infected chickens compared to healthy ones. Similarly, Attia et al (2018) mentioned that the serum levels of tilmicosin were markedly higher in healthy chickens than in M. gallisepticum and Escherichia coli infected ones.…”