الفهرس 
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Abstract
The present work was carried out to reveales some pharmacokinetic aspects of difloxacin in both healthy and infected chickens.The bioavailability of difloxacin following oral adminstration were estimated in both healthy and infected chcikens. The protien binding percent of the drug to serum was also estimated. Determination of MIC and MBC of the drug also estimated.
The present study was carried out on 18 chickens . These birds were obtained from poultry farm in Fayoum Governorate with an avearage body weight from 1.800 to 2. 00 kg and proved to be clinically healthy.
In the first experiment six clinically healthy chickens were given difloxacin hydrochloride 10mg/kg b.wt. as a single intravenious dose (through wing vein) and single oral dose (intra-crop route) with two weeks washout period between each route.
Blood samples were collected 5, 10, 15 and 30 min. 1, 2, 4, 6, 8, 12 and 24 hours post injection. The concentration of the drug in serum sample was determined using the microbiological assay method.
In the second experiment, 12 chickens divided into two groups (6 chickens in each). Each chicke infected with avian pathogenic E.coli O78.thats increasing its virulence through E.coli injection into one day old chicks then heart isolated on macConkey agar media as a specific media for E.coli.
The minimum inhibitory concentration and minimum bactericidal concentration of the drug to Escherchia.coli (ATCC 25922) was also investigated.
1- Intravenous injection of difloxacin in healthy chickens :
After intravenous injection of difloxacin in a dose of 10 mg /kg b.wt. , the drug was showed a high serum level (8.02 ug / ml) 5 min post injection, then the concentration decreased gradually till reached its minimum level (0.15 ug/ ml) at 24 h post –injection. The present data revealed that the serum concentration time curves of difloxacin were best described by a two compartment –open model.
The drug was rapidly distributed with a distribution half-life (t 0.5 α) of 5.84 h and apparent volume of distribution calculated by extrapolation Vd(B), area Vd(area), pseudo equilibrium Vc and steady state Vd(ss) methods were 3.89, 3.95, 0.81 and 3.14 l/kg respectively. The drug was distributed in the central compartment with a volume of distribution (Vc) 0.81 l/kg., indicating that the drug is highly distributed in extra vascular tissues.
The drug was rapidly eliminated with a half-life of elimination (t0.5β) of 3.7 and the body clearance of difloxacin (ClB) was 0.65 ml/kg/h. The mean residence time (MRT) was 4.73 h.
2- Oral administration of difloxacin in healthy chickens :
Following oral administration of difloxacin in a single dose of 10 mg/kg b.wt., the drug was detected in serum 0.25 h post injection (0.06 ug/ ml) and it continued to increase gradually thereafter and was reached its maximum level 1.46 ug/ml at 2 h post injection, then started to decrease gradually till reached its lowest concentration 0.09 ug/ ml at 24 hours. It was rapidly absorbed with a half-life of absorption (t0.5ab) of 0.57 h., while its elimination half-life (t0.5el) was 4.7 h .The systemic bioavailability of difloxacin following oral administration was 86.24 %. This indicated good absorption of the drug from this site of injection.
The in vitro protein binding percent to serum was 3.99 %.
3- Intravenous injection of difloxacin in infected chickens:
After intravenous injection of difloxacin in a dose of 10 m g/kg b.wt. in infected chickens the drug was showed a high serum level (4.67 ug/ml) 5 min. post injection, then the concentration decreased gradually till reached its minimum level (0.07 ug/ ml) at 24 h post –injection. The present data revealed that the serum concentration time curves of difloxacin were best described by a two compartment –open model.
The drug was rapidly distributed with a distribution half-life (t0.5 α) of 3.3 h and apparent volume of distribution calculated by extrapolation Vd(B), area Vd(area), pseudo equilibrium Vc and steady state Vd(ss) methods were 11.96, 11.03, 0.9 and 9.25 L/kg respectively. The drug was distributed in the central compartment with a volume of distribution (Vc) 0.9 L/kg., indicating that the drug is highly distributed in extra vascular tissues.
The drug was rapidly eliminated with a half-life of elimination (t0.5β) of 6.42 and the body clearance of difloxacin (ClB) was 1.14 ml/kg/h. The mean residence time (MRT) was 8.34 h.
4- Oral administration of difloxacin in infected chickens:
Following oral administration of difloxacin in a single dose of 10 mg /kg b.wt., to the infected chickens the drug was detected in serum 0.25 h post injection (0.028 ug ml-1) and it continued to increase gradually thereafter and was reached its maximum level 1.19 ug / ml at 2 h post injection, then started to decrease gradually till reached its lowest concentration 0.047 ug/ml at 24 hours. It was rapidly absorbed with a half-life of absorption (t0.5ab) of 0.77 h., while its elimination half-life (t0.5el) was 3.42 h. The systemic bioavailability of difloxacin following oral administration was 90.6 %.
6- In –vitro activity of difloxacin against E.coli :
Escherchia.coli ATCC 25922 was sensitive to difloxacin. The minimum inhibitory concentrations of difloxacin that prevent the growth of the microorganism, was 0.02 ug/ml while the minimum bactericidal concentration of the drug that kill them was 0.04 ug/ml.