الفهرس 
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Abstract
The pharmacokinetics of norfloxacin following single intravenous or oral and repeated oral administrations was studied in forty eight Hubbard chicken (27 normal and 21 experinmentally Escherichia coli infected chicken) and the chicken were divided into 5 groups. The pharmacokinetic parameters, drug clearance, bioavailability values and tissue residues were evaluated. The protein binding percent of norfloxacin was estimated microbiologically in vitro. The pharmacokinetic parameters following a single intravenous injection of 10 mg norfloxacin/kg b.wt. in normal chicken revealed that the drug obeyed a two compartments open model. The disposition kinetics of norfloxacin following a single intravenous injection revealed that, the distribution phase (α) equal to 4.65 ± 0.03 h-1 with a distribution half-life [t0.5(α)] equal to 0.149 ± 0.001 h. Norfloxacin was transferred from central to the peripheral compartment at a low rate (K12= 1.40 ± 0.02 h-1) than its passage from the peripheral to the central compartment (K21= 2.94 ± 0.06 h-1). The volume of distribution (Vdss) was 2223.17 ± 65.62 ml/kg. Norfloxacin was eliminated in current study following a single intravenous injection with elimination half-life [t0.5(β)] equal to 4.71 ± 0.06 h. The total body clearance (CLtot) was 1.72 ± 0.02 ml/kg/min. Following single oral administration, norfloxacin was rapidly and efficiently absorbed throught gastrointestinal tract of broiler chicken as the absorption half life (t0.5ab: 0.57 ± 0.01 h). The pharmacokinetic parameters following a single oral administration of ofloxacin revealed that the apparent first order absorption rate constant (Kab) was (1.21 ± 0.02 h-1). The calculated maximum serum concentration [Cmax] was (3.87 ± 0.04 µg/ml) reached at maximum time [tmax] at about (2.09 ± 0.03 h) and the calculated minimal serum concentration of norfloxacin [Cmin] was (0.23 ± 0.01 µg/ml) indicating better absorption of norfloxacin. Norfloxacin was eliminated at a rate (Kel) equal to 0.12 ± 0.001 h-1 with elimination half life [t0.5(β) ] of 5.72 ± 0.05 h. Norfloxacin was cleared by all clearance processes [CLtot] in the body at rate equal to 0.241 ± 0.003 L/kg/h indicating the tendency of chicken to eliminate of norfloxacin in slow rate. The area under serum norfloxacin concentration time curve following a single oral administration (AUC) oral was compared with the area under the serum norfloxacin concentration time curve following a single intravenous injection (AUC) i.v. in the same chicken. This comparison revealed a mean systemic oral bioavailability of 66.89 ± 1.95 % indicating moderate absorption of norfloxacin from oral site.In present study norfloxacin was bound in- vitro with the chicken’s serum protein at percentage equal to 10.37 ± 0.22 %. Oral administrations of 10 mg norfloxacin / kg.b.wt once daily for five consecutive days in normal and E.coli infected chicken revealed a significant decrease in serum norfloxacin concentrations at all time sampling in E.coli infected chicken than in normal chicken. The pharmacokinetic parameters of norfloxacin after repeated oral administration in normal and E.coli infected chicken, the apparent first order absorption rate constant (Kab) was significantly increase in E.coli infected chicken than in normal chicken following administration of all doses. The elimination half-lives [t0.5(β)] were significantly increase in E.coli infected chicken than in normal chicken. Norfloxacin was cleared by all clearance processes (CLtot) in the body at high significant rates in E.coli infected chicken than in normal chicken.Tissues residues of norfloxacin in slaughtered normal and E.coli infected chicken following the oral dosage regimen (10 mg/kg b.wt. once daily for five consecutive days could not be detected by microbiological assay in all tested tissues except in lung, liver, and kidneys in chicken at 48 hours post last administration, so the chicken must not be slaughtered before 3 days.The current investigation concluded that repeated oral administration of 10 mg/kg b.wt. norfloxacin once daily for 5 consecutive days would provide an effective concentration against E.coli in broiler chicken. The oral bioavailability of norfloxacin is moderate so it is recommended to be used against enteric and systemic E.coli. Treated chickens must not be slaughtered before 3 days from last dose of repeated administration of norfloxacin to withdraw the drug residues from liver, kidneys and lungs of treated chickens.