الفهرس 
english coverOnly 14 pages are availabe for public view
 |  | from | 116 |  |  |
| | | from | 116 | | |
Abstract
The influence of probiotics on the pharmacokinetics and tissue residue of difloxacin in apparently healthy and Mycoplasma gallisepticum infected chickens was studied after intravenous and oral administrations at a dose of 10 mg/kg.b.wt. The chickens were classified into two main groups each one subdivided into 6 subgroups: the first one was used for studying the impact of probiotics on the pharmacokinetic features and tissue residues of difloxacin in healthy chickens. The 6 subgroups are allocated into 4 subgroups for studying the effect of probiotics on the pharmacokinetics of difloxacin in healthy chickens (2 with and 2 without probiotic treatment). The other two subgroups were used for studying the effect of probiotic on difloxacin tissue residues. The second group was used for studying the impact of probiotics on the pharmacokinetic features and residues levels of difloxacin in Mycoplasma gallisepticum-experimentally infected chickens in which the 6 subgroups were allocated into 4 subgroups(2 with and 2 without probiotic treatment) for studying the effect of probiotic on the pharmacokinetic of difloxacin in MG infected chickens. The other two subgroups were used to study the effect of probiotic on difloxacin tissue residues. Probiotic was given from day 5 after hatching to day 21 of age and difloxacin was given after overnight fasting of the last probiotic dose either IV or oral in a single dose of 10 mg/kg. Difloxacin residues were estimated after 5 consecutive days of oral administration and the edible organs (muscle, liver, kidney and gizzard) were collected from slaughtered birds 1, 3, 5 and 7 days after the last dose. Plasma concentrations and tissue residues of difloxacin were estimated by using HPLC technique. The plasma difloxacin concentrations-time course was best fitted to a 2 compartment open model. Following intravenous administration, plasma concentration of difloxacin at zero time was significantly higher (12.09±0.07 vs 11.82±0.1h) in probiotic-pretreated chickens as compared to non-treated birds and a significantly prolonged half-life (4.09±0.03 vs 3.75±0.02 h) in probiotic-pretreated chickens as compared to non-treated birds . The volume of distribution and the clearance rate although achieved higher values, however, the significant difference did not occur. The areas under curves (AUC0-t, AUC0-inf, AUMC) and the MRT were much higher in probiotic-pretreated chickens. The elimination half-life (t½β) of difloxacin in MG-infected chickens (4.55±0.05 h) was significantly shorter than probiotic treated MG-infected birds (4.75±0.09 h) and the volume of distribution at steady state (vss) was larger in the infected chickens as compared to probiotics-pretreated MG-infected one (4.16±0.07 and 4.05±0.07 mg/(μg/ml, respectively). Following oral administration, the drug reached its peak plasma concentrations (Cmax) of 1.8 ± 0.19 µg/ml at maximum time (tmax) of 2.66 ± 0.06 h in probiotic non treated normal chickens, while in probiotic-pretreated healthy chickens, the Cmax 2.31± 0.17 µg/ml attained at tmax of 2.5 ± 0.03h. In the infected group, the MRT was significantly shorter in infected chickens pretreated with probiotics (5.36±0.03 h) as compared with non-treated one (5.71±0.09 h P<0.05). After repeated oral administration of difloxacin at a dose of 10 mg /kg.b.wt once daily for 5 successive days, difloxacin was detected in all edible tissues up to the 3rd day and in the liver and kidney for 5 days after the last day of administration. The liver and kidney contained the highest concentrations of difloxacin. The residues of difloxacin 24 hours after the last oral dose was lower than the recommended MRLs. In conclusion, the pharmacokinetic parameters of difloxacin were altered due to concurrent administration of probiotics and the withdrawal period of difloxacin may be re-evaluated when concurrently administered with probiotics.