الفهرس 
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Abstract
In the present work, the effect of vaccination with lysate vaccine on the disposition kinetics of enrofloxacin and tylosin following intravenous and intramuscular injection in rams was studied. Bioavailability of both drugs were calculated in non vaccinated and vaccinated rams after a single intramuscular dose.
6.1. Enrofloxacin:
Following a single intravenous injection of 2.5 mg enrofloxacin/kg b.wt. in non vaccinated and vaccinated rams, the drug could be detected therapeutically for 24 hours with values equal to 0.33 ug/ml in non vaccinated rams and 0.5 pig/m1 in vaccinated rams. The serum concentration time curve of enrofloxacin following intravenous injection showed that the drug obeyed a three compartments open model. The pharmacokinetic parameters of enrofloxacin after a single intravenous injection in vaccinated rams revealed some significant variations than in non vaccinated rams. These variations represented by higher distribution phase (a = 1.2 III) in vaccinated than in non vaccinated rams (a = 1.2 11’), while distribution half life (to.5(co) decreased in vaccinated (0.46 h) than in non vaccinated rams (0.61 h). The volume of distribution of control compartment (V1) was decreased significantly in vaccinated rams (0.127 L/kg) than in non vaccinated ones (0.206 L/kg) whereas the total body distribution calculated by extrapolation (V2), area (V3) and steady state (Vass) methods revealed significant decrease in vaccinated in comparison to those in non vaccinated rams. These variations in distribution of enrofloxacin between non vaccinated and vaccinated rams might be attributed to the
directions of most body function to the antigen antibody reactions in vaccinated rams as well as at the beginning of immunogenesis. Enrofloxacin was eliminated after intravenous injection with a half life (t0.5()) values of 6.62 h in non vaccinated rams and 5.34 h in vaccinated ones. It was eliminated from the body (K10) at a rate higher in vaccinated (0.35 11) than in non vaccinated rams (0.3111).
The serum concentrations of enrofloxacin following a single and repeated intramuscular injection of 2.5 mg/kg b.wt. in non vaccinated and vaccinated rams, pecked two hours after injection with a higher significant value in vaccinated than in non vaccinated rams. This observation might attributed to the lower concentration of total protein a.nd albumin fraction as a result of vaccination.
The disposition kinetics following a single intramuscular injection of 2.5 mg/kg b.wt. in non vaccinated and vaccinated rams, pecked two hours after injection with a higher significant value in vaccinated than in non vaccinated rams. This observation might be attributed to the lower concentration of total protein and albumin fraction in vaccinated rams.
The disposition kinetics following a single intramuscular injection of 2.5 mg enrofloxacin/kg b.wt. in non vaccinated and vaccinated rams revealed significant variations in some parameters represented by higher significant values in maximum serum concentration(Cmax) and maximum serum concentration at steady state 1,-- max ) in vaccinated than in non vaccinated rams. 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. The mean systemic bioavailability following intramuscular injection was increased in vaccinated.(75.63%) than in non vaccinated one (71.66%).
During repeated intramuscular injection enrofloxacin showed a cummulative serum levels at all times of samplings after each dose if compared to the first dose. The calculated pharmacokinetic parameters in vaccinated rams were statistically changed when compared to those in non vaccinated rams. These variations might be attributed to reconstruction activation and hyperplasia of the lymphoreticular cells during the process of immunogenesis.
Repeated injection of enrofloxacin 2.5 mg/kg b.wt. daily for five consecutive days decreased the titer of antibodies after the fourth, fifth and sixth days. So we advised to stop the application of enrofloxacin during maximum titers of lysate vaccine.
6.2.Tylosin:
Following single intravenous injection of 10mg tylosin/kg b.wt. in non vaccinated and vaccinated rams, tylosin could be detected therapeutically 24 hours post intravenous dose with a value equal to 0.12 μg/ml in non vaccinated rams and 0.17 }.1g/m1 in vaccinated rams. The serum concentration-time curve of tylosin 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 tylosin revealed a distribution half lives (t0.5(co) which was higher in vaccinated rams (0.14 h)than in non vaccinated rams (0.10 h). The total body distribution calculated by extrapolation (Vd(B)) and area (Vd(area)) methods revealed significant increase in vaccinated rains (0.48 and 0.44 L/kg, respectively) if compared to the non vaccinated rams (0.614 and 0.558 L/kg, respectively).
These variations in distributions of tylosin between non vaccinated and vaccinated rams might be attributed to the directions of most body function to the antigen antibody reactions in vaccinated rains as well as at the beginning of immunogenesis.
Tylosin eliminated after intravenous injection with a half lives (t0.5(0)) values increased in vaccinated rains (3.52 h) than in non vaccinated rams (3.47 h). Tylosin cleared by all clearance processes in the body (Choi) at a rate higher in vaccinated (0.45 hour) than in non vaccinated rams (0.4 hour).
The serum concentrations of tylosin following a single and repeated intramuscular injection of 10 mg/kg b.wt. in non vaccinated and vaccinated rams, pecked 4 hours after injection with a higher significant value in vaccinated than in non vaccinated rams. This phenomena might be attributed to the lower concentration of total protein and albumin fraction in vaccinated than in non vaccinated rams as well as the direction of most of the body function to the antigen-antibody reaction induced by vaccination.
Intramuscular injection of 10 mg tylosin/kg b.wt. in non vaccinated and vaccinated rams revealed significant changes in some parameters represent in higher significant values in maximum serum concentration (C.) and maximum serum concentration at steady state (Cmax) in vaccinated than in non vaccinated rams. 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 rains. The biological half lives (t0.503)) were ranged from 3.7 to 3.8 h (non vaccinated rams) and from 3.68 to 3.98 hours (vaccinated rams). The mean systemic bioavailability following intramuscular injection was significantly increased in vaccinated (63.5 %) than non vaccinated rams (37.7%).
During repeated intramuscular injection of 10 mg tylosin/kg b.wt. once daily for five consecutive days; tylosin serum concentration increased significantly at all time of sampling in vaccinated than in non vaccinated rams. 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 rams. The calculated pharmacokinetic parameters in vaccinated rams were statistically changed when compared to that in non vaccinated rams. These might be attributed to reconstuction, activation and hyperplasia of lymphoreticular cells during immunogenesis processes
in vaccinated rams.
Repeated injection of tylosin 10 mg/kg b.wt.daily for five consecutive days decreased the titer of antibiotics after the fourth and fifth days. So we advised to stop the application of tylosin during the maximum titer of lysate vaccine.