الفهرس 
Materials and MethodsOnly 14 pages are availabe for public view
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Abstract
The pharmacokinetics of ofloxacin following single intravenous, single oral and repeated oral administrations were studied in forty eight broiler chickens (27 non vaccinated and 21 vaccinated chickens) and the chickens were divided into 5 groups. The pharmacokinetic parameters, drug clearance, bioavailability, tissue concentrations and the protein binding percent of ofloxacin were estimated microbiologically in vitro.
Following a single intravenous injection of 20 mg ofloxacin/kg b.wt. in non vaccinated chickens, ofloxacin could be detected therapeutically in serum till 24 hours post injection with mean value of 0.32 µg/ml. Also the pharmacokinetic parameters revealed that the drug obeyed a two compartments open model. The disposition kinetics of ofloxacin following a single intravenous injection revealed that, the distribution phase (α) equal to 2.32 h-1 with a short distribution half-life [ t0.5(α)] equal to 0.29 h, suggesting rapid distribution of ofloxacin in chicken’s tissues and fluids. Ofloxacin was transfered from central to the peripheral compartment at a higher rate (K12= 1.28 h-1) than its passage from the peripheral to the central compartment (K21= 0.75 h-1). The volume of distribution calculated by steady state method (Vdss) was 3.53 ml/kg, which indicated wide distribution and good tissue penetration of ofloxacin. The elimination half life (t0.5β) valued 5.01 h.
Following a single oral administration of 20 mg ofloxacin/ kg. b.wt. the drug reached its maximum serum concentrations (3.01 µg/ml) at 3.05 hours and could be detected in serum in a therapeutic level 0.49 µg/ml for 24 hours. The pharmacokinetic parameters following a single oral administration of ofloxacin revealed that the apparent first order absorption rate constant (Kab) was (0.76 h-1). The calculated maximum serum concentration [Cmax] was (3.01 µg/ml) reached its maximum time [tmax] at about (3.05 h) and the calculated minimal serum concentration of ofloxacin [Cmin] was (0.49 µg/ml) indicating better absorption of ofloxacin. Ofloxacin was eliminated at a rate (Kel) equal to 0.10 h-1 with elimination half life [t0.5(el) ] of 6.68 h.
The area under serum ofloxacin concentration time curve following a single oral administration (AUC) oral was compared with the area under the serum ofloxacin concentration time curve following a single intravenous injection (AUC) i.v. in the same chickens. This comparison revealed a mean systemic oral bioavailability of 95.76 percent indicating high absorption of ofloxacin from oral site.
In the present study ofloxacin was bound in- vitro with the chicken’s serum protein at a percentage equal to 15.51%.
Oral administrations of 20 mg ofloxacin / kg.b.wt once daily for five consecutive days in non vaccinated and vaccinated chickens revealed a significant increase in serum ofloxacin concentrations at all time sampling in vaccinated chickens than in non vaccinated chickens. Also revealed that the apparent first order absorption rate constant (Kab) was significantly increased in vaccinated chickens than in non vaccinated chickens following administration of all doses. The elimination half-lives [t0.5(el)] were significantly increased in vaccinated chickens than in non vaccinated chickens.
Tissues residues of ofloxacin in slaughtered non vaccinated and vaccinated chickens following the oral dosage regimen (20 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 24 and 48 hours post last administration, so the chickens must not be slaughtered before 3 days.