الفهرس 
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Abstract
In the present work, the effect of vaccination with Newcastle disease virus vaccine (LaSota strain) on the disposition kinetics of aminosidine and lincomycin following intravenous and intramuscular injection in non vaccinated and vaccinated chickens were studied. Bioavailability of both drugs were calculated in non vaccinated and vaccinated chickens after a single intramuscular dose. The in vitro protein binding percent of aminosidine and lincomycin were determined microbiologically as well as detection of both drug residues in slaughtered non vaccinated and vaccinated chicken tissues.
Following a single intravenous injection of 20 mg aminosidine kg b. wt in non vaccinated and vaccinated chickens, aminosidine could be detected therapeutically 12 hours post-intravenous dose with a values equal to 2.15 ug/m1 in non vaccinated chickens and 3.00 ).1g/m1 in vaccinated chickens. The serum concentration-time curve of aminosidine following intravenous injection showed that the drug obeyed a two-compartments open model. In this open system model, blood should have been sampled at very frequent intervals during early distribution phase. The phrmacokinetic parameters of aminosidine after a single intravenous injection in non vaccinated chickens revealed some significant variations than in vaccinated chickens. These variations represented by lower distribution phase (a = 3.69 h-1) in non vaccinated
than in vaccinated chickens (a = 6.83 If), while distribution half-life {t0.5(m] increased significantly in non vaccinated (0.19 h) than in vaccinated chickens (0.11 h). The volume of distribution to central
compartment (V\c) was increased significantly in non vaccinated chickens (0.13 AO than in vaccinated ones ( 0.09 1/kg) whereas the
total body distribution calculated by extrapolation [Vdo-j, area [Vd(areaj
and steady state [Vdss] methods revealed significant changes in non vaccinated in comparison to those in vaccinated chickens. These variations in distribution of aminosidine between nonvaccinated and vaccinated chickens might be attributed to the directions of most body function to the antigen antibody reactions in vaccinated chickens as well as at the beginning of immunogenesis there was some increase in the antibiotic level. Aminosidine eliminated after intravenous injection with
a half-life [to.5(p)] values of 2.53 h in non vaccinated chickens and 2.45 h in vaccinated ones. While it cleared by all clearance processes in the body (Cltot) at a rate significantly higher in non vaccinated (0.60 ml/kg/min.) than in vaccinated chickens (0.45 mlikgimin.). The serum concentrations of aminosidine following a single and repeated intramuscular injection of 20 mg/kg b.wt in non vaccinated and vaccinated chickens, peaked one hour after injection with a lower significant value in non vaccinated than in vaccinated chickens. This observation might be attributed to the lower concentration of total protein and albumin fraction in vaccinated than in non vaccinated
chickens.
The disposition kinetics following a single intramuscular injection of 20 mg aminosidine /kg b.wt in non vaccinated and vaccinated chickens revealed significant variations in some parameters represented by lower significantly values in maximum serum concentration (cmax)
and maximum serum concentration at steady state (c\ma,) in non vaccinated than in vaccinated chickens. 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 in vaccinated than in nonvaccinated chickens. The mean systemic bioavailability following intramuscular injection was significantly increased in non vaccinated (68.43 %) than in vaccinated one (58.27 %).
During repeated intramuscular injection, aminosidine showed a cummulative effects in non vaccinated chickens, whereas there were significant increases in aminosidine serum concentrations at all time of samplings after each dose if compared to the first dose. The calculated phartnacokintetic parameters in non vaccinated chickens were statistically changed when compared to those in vaccinated chickens.
Tissue residues of aminosidine in slaughtered non vaccinated and vaccinated chickens following the dose regimen (20 mg aminosidne /kg b.wt twice daily for five consecutive days) could not be detected in brain, breast and thigh muscles of non vaccinated and vaccinated chickens. Aminosidine persisted in both lung and heart tissues till 4 hours after administration in non vaccinated and vaccinated chickens. On other hand, aminosidine residues were assayed in serum, fat and skin till 12 hours but in kidney till 24 hours. Aminosidine residues showed a lower significant concentration in some tissues of vaccinated chickens than in non vaccinated chickens. These variations might be attributed to reconstruction, activation and hyperplasia of the lymphoreticular cells during the process of immuogenesis.
The in vitro protein binding percent of aminosidine in chickens serum was 3.27 %.
The geometric mean values of haemagglutination antibody titers . of vaccinated chickens revealed that there was no significant changes before and after intravenous or intramuscular injection of aminosidine. Following repeated intramuscular administration of 20 mg aminosidine/ kg b. wt twice daily for five consecutive days in vaccinated chickens, the geometric mean values of haemagglutination titre decreased significantly at fourth and fifth days following aminosidine injection.
Following a single intravenous injection of 50 mg lincomycin / kg b. wt in non vaccinated and vaccinated chickens, lincomycin could be detected therapeutically 6 hours post-intravenous dose with a value equal to 1.18 ug/ml in non vaccinated chickens and 1.02 1.1g/m1 in vaccinated chickens. The serum concentration-time curve of lincomycin following intravenous injection showed that the drug obeyed a two-compartments open model. In this open system model, blood should have been sampled at very frequent intervals during early distribution phase. Intravenous injection of lincomycin revealed a distribution half-
lives [t0.05(c)] which was significantly lower in non vaccinated chickens (0.10 h) than in vaccinated chickens (0.16 h).
The total body distribution calculated by extrapolation [Vd(p)],
area [Vd(ared and steady state [Vd„) methods revealed significant increases in non vaccinated chickens (2.55, 2.00 and 1.61 1/kg, respectively) if compared to the vaccinated chickens(1.93, 1.53. and 1.25 Vkg, respectively). These variations in distribution of lincomycin between nonvaccinated and vaccinated chickens might be attributed to the directions of most body function to the antigen antibody reactions in vaccinated chickens as well as at the beginning of immunogenesis there was some increase in the antibiotic level. Lincomycin eliminated after
intravenous injection with a half-lives [tan)] values significantly
increased in non vaccinated chickens (1.46 h) than in vaccinated chickens (0.5:5 h). Lincomycin cleared by all clearance processes in the body (CL,tot)at a rate significantly higher in non vaccinated (4.19
mlikgimin.) than in vaccinated chickens (1.27 ml/kgimin. ).
The serum concentrations of lincomycin following a single and repeated intramuscular injection of 50 mg lincomycin /kg b.wt in non vaccinated and vaccinated chickens, peaked 0.25 hour after injection with a lower significant value in non vaccinated than in vaccinated chickens. This phenomena might be attributed to the lower concentration of total protein and albumin fraction in vaccinated than in non vaccinated chickens, as well as the direction of most of the body function to the antigen-antibody reaction induced by vaccination.
The pharmacokinetic profile following a single intramuscular injection of 50 mg lincomycin /kg b.wt in non vaccinated and vaccinated chickens revealed significant changes in some parameters represented in lower significant values in maximum serum concentration (cr.) and maximum serum concentration at steady state (c\max) in non vaccinated
than in vaccinated chickens. 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 in vaccinated than in nonvaccinated chickens. The biological half-lives
[t0.50)] increased significantly in non vaccinated chickens (1.56 h) than in vaccinated chickens (1.37 h).
The mean systemic bioavailability following intramuscular injection did not significantly changed between non vaccinated (67.30%) and vaccinated chickens (66.04 ’,vo).
During repeated intramuscular injection of 50 mg lincomycin /kg b.wt 6 hours interval daily for five consecutive days, lincomycin serum concentration increased significantly at all time of sampling in vaccinated than in non vaccinated chickens 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 in vaccinated than in nonvaccinated chickens.
The calculated pharmacokinetic parameters in non vaccinated chickens were statistically changed when compared to those in vaccinated chickens. These might be attributed to reconstruction, activation and hyperplasia of lymphoreticular cells during immunogenesis processes in vaccinated chickens.