الفهرس 
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Abstract
In the present work , studying of the pharmacokinetic parameters following intravenous and oral administration of 5 mg /kg body weight danofloxacin ,3 times daily for five days in non vaccinated and vaccinated chicken with Newcastle virus vaccine were studied .Bioavailability in non vaccinated chicken were calculated . Drug residues in non vaccinated and vaccinated chicken with Newcastle virus vaccine were determined . The effect of danofloxacin on the immunity response of chicken vaccinated against Newcastle disease were investigated .
6.1. Pharmacokinetic studies of danofloxacin :
Following a single intravenous injection of 5 mg / kg body weight in non vaccinated chicken ,the drug could be detected therapeuticaly for 12 hours with value equal to 0.033 lig / ml The serum concentration time curve of danofloxacin following intravenous injection showed that the drug obeyed a two compartement open model . The dispostion kinetics of danofloxacin following a single intravenous injection revealed a considerable rapid distribution phase ( a ) equel to 3.75 with a distribution half life { t 0.5( a) equal to 0.190 h . The volume of distribution of danofloxacin of the central compartment ( c ) was 1983.4 ml/kg whereas the total body distribution calculated by the extrapolation { V d (3) }, area { V d (area) }, and steady — state { V ass} method were 1539.26, 24024,15415.90 ml/kg respectively . Danofloxacin was transfered from central to peripheral compartment (K 11) at slower rate (2.11111) than its passage from the preipheral to the central compartment (K21) which equal to 0.311 h-1 . On the otherhand ,danofloxacin eliminated from the central compartment with elimination rate constant equal to ( K el = 1.41 11’) . Danofloxacin eliminated after intravenous injection with half -life { t 0.5( 13)} value of 5.80 h and cleared by all processes in the body at a rate of ( CL tot ) 3.94 ml/kg/min .
The serum concentrations of danofloxacin following single and repeated oral administration of 5 mg/kg body weight in non vaccinated and vaccinated chicken peaked one and two hours respectively after adminstration with a higher significant values in vaccinated than in non vaccinated chicken . This observation might be attributed to the lower concentration of total protein and albumin fraction as a result of vaccination .
The disposition kinetics following a singal oral administration of 5 mg / kg body weight danofloxacin in non vaccinated and vaccinated chicken revealed significant variation in some parameters represented by higher values in maximum serum concentration (C.) and maximum serum concentration at steady state (C\ max) in vaccinated than non vaccinated chicken . This observation might be attributed to the increase in the antibiotic level during the process of immunogenesis and the lower concentrations of total serum protein and albumin fraction as a result of vaccination .
During repeated oral administration of danofloxacin , a commulative serum levels at all times of sampling after each dose if compared to the first dose were recorded . The calculated pharmacokinetic parameters in vaccinated chicken were statistically changed when compared to those in non vaccinated chicken . These variations might be attributed to reconstruction activation and hyperplasia of the lymphoreticular cells during the process of immunogensis .
Tissue residues in slaughtered vaccinated chicken were significantly higher than that of non vaccinated chicken . This might be attributed to the lower concentration of total serum protein and albumin fraction as a result of vaccination .
Repeated oral administration of 5 mg / kg body weight for five days did not show any significant change in the antibody titre but with no protective effect of chicken against Newcastle disease . It is advised to stop the application of danofloxacin either at the same time with vaccination or during the maximum titres of Newcastle virus vaccine .
6.2. Immunological effect of danofloxacin :
Effect of danofloxacin on the immune response ( humoral and cell mediated immunity ) of breeder chicken vaccinated with inactivated Newcastle virus vaccine was investigated .
The effect of drug on the cellular immune response was determined using total leucocytic count and differintial leucocytic count , relative weight of lymphoid organs ( spleen , bursa of Fabricus and thymus gland ) and histopathological examination of lymphoid organs .
The effect of danofloxacine on humoral immune response was determined using hemagglutination inhibition titre , estimation of the level of total serum protein , albumin , globulin ,albumin /globulin ratio and globulin fractions ( alpha , beta and gamma globulins ) . The whole impact on the immune response was evaluated by estimation of the protection against challenge with Newcastle disease virus ( VVND74 ).
Daily administration of danofloxacin for five days in a concentration of 5 mg/kg body weight and then vaccinated with Newcastle virus vaccine did not have effect on total leucocytic count and differintial leucocytic count excpet at third and fourth week , where a reduction in lymphocytes with increase in heterophils were reported . Danofloxacin did not have significant effect on the relative weight of lymphoid organs ( spleen , bursa of Fabricus and thymus gland ) . Danofloxacinand then vaccination did not cause any significant histopathological changes in the lymphoid organs (spleen ,bursa of Fabricius and thymus gland ). from the above mentioned data it could concluded that danofloxacin (5 mg/kg body weight) and then vaccinated with Newcastle virus vaccine intraocullarly did not affect the cellular immune response .
Oral administration of 5 mg/kg body weight for five days and then vaccinated with Newcastle virus vaccine did not cause any significant effect on hemagglutination inhibition titre .Danofloxacin did not provoke any significant effect on total serum albumin , level of albumin , total globulin and albumin /globulin ratio The protection against challenge with Newcastle disease virus (VVNDV74) was 80% in chicken treated with danofloxacin and then vaccinated with Newcastle virus vaccine where it nearly resemble that of vaccinated non treated group . Oral administration of danofloxacin either with or after 10 days of vaccination with Newcastle virus vaccine resulted in significant reduction in total leucocytic count and heterophils monocytes and basophils percent began at second , third and fourth week . There was also significant increase in lymphocytes percent began at the second week and lasted the whole time of the experiment . Danofloxacin either with or after 10 days of vaccination significantly reduced the relative weight of lymphoid organs ( spleen , bursa of Fabricius and thymus gland ) . Histopathological changes occurred in spleen , bursa of Fabricius and thymus gland which characterized by lymphoid depletion , focal area of coagulative necrosis and the splenic blood vessels showed sever congetion , hemorrahage and thrombosis .
Chicken administred 5 mg/kg body weight either with or after 10 days of vaccination showed significant decrease in hemagglutination inhibition titre began in the second week post vaccination . There was reduction in serum total protein , albumin , globulin and globulin fractions .
Protection percent against challenge with Newcastle virus (VVNDV74) in chicken orally administred 5 mg /kg body weight with or after 10 days of vaccination was reduced to 60 and 40 % respectively comparable to 100 % in vaccinated non terated chicken.
It is concluded that danofloxacin must not be administred either with or after 10 days of vaccination as it significantly decreased both cellular and humoral immune respose .Therapy with danofloxacin was not recommended during vaccination program.