الفهرس 
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Abstract
In the present work, the pharmacokinetic profiles of netilmicin and vancomycin were studied following intravenous and intramuscular adminsitration in normal chickens. Bioavailabilities of both drugs were calculated following a single intramuscular administration. The protein binding percents was also determined microbiologically in - vitro. Antibiotic residues in normal chicken tissues were detected following repeated
intramuscular administration .
6.1. Netilmicin :
Following single intravenous injection of 10 mg netilmicin /kg.b.wt. in normal chickens, the drug obayed a two-
compartments open model with half -life of distribution[t0.5 (a)]
of 0.30 f 0.03 hours. The volume of distribution of central compartment (Vc) was 0.140 ± 0.004 t,/kg and those calculated by extrapolation [Vd(B)1 , area I Vd(areall and steady-state [Vdss] methods were 0.319 ± 0.01, 0.288 ± 0.01, and 0.264 ±
0.009 L/kg, respectively. The elimination half-life [t0.5 (120)
was 3.89 ± 0.06 hours.The overall elimination rate constant (0) was 0.17 ± 0.003 h-1 and total body clearance was 0.41 ± 0.010 ml/kg/min. Following a single intramuscular injection of netilmicin (10 mg/ kg. b. wt. ) in normal chickens a maximum serum concentration rmax. = 17.98 + 3.32 ug / ml] was recorded at two hours with half-life of absorption (t0.5 (am) valued with 0.63 ± 0.09 hour. The elimination half-life (t0.5 (a)) was 4.02 ± 0.13 hour. The bioavailability after single intramuscular injection was 27.29 ± 4.77%. During repeated intramuscular injection of 10 mg netilmicin/ kg.b.wt twice daily for five consecutive days in normal chickens ,the highest serum drug concentration was achieved after two hours post each dose. The tissue concentrations , 12 hours after the last dose of repeated intramuscular injection were 46.66 ± 2.84 ug/g in liver, 41.86 ± 0.95 ug/g in kidney, 21.5 ± 0.81 ug/g in lung, 11.33 ± 0.44 ug/g in gizzard, 15.33 ± 1.20 ug/g in heart, 11.50 ± 0.28 ug/g in fat, 10.00 ± 0.86 ug/g in thigh muscle and 9.83 ± 1.01 ug/g in breast muscle. The drug persisted in liver and kidney for 96 hours after the last administration. Netilmicin disappeared from all body tissues 120 hours of the last dose of repeated intramuscular administrations. The in - vitro protein binding percent of netilmicin was 7.45 ± 0.7 %.
6.2. Vancomycin:
Following a single intravenous injection of 30 mg/kg b.wt. in normal chickens the drug obayed a three- compartments open
model with half-life of distribution [t0.5 (0] of 0.204 ± 0.026
hour. The volume of distribution of the central compartment (Vi),first peripheral (V2) , second peripheral (V3) and that calculated bysteady state methods (Vdss) were equal to 224.81 ± 11.92 ml/kg , 345.54 ± 26.83 ml/kg , 121.32 ± 4.80 ml/kg , and 691.67 ± 33.93 ml/kg, respectively. The total body clearance
(CLtot) was 3.81 ± 0.15 ml/kg/min.
Following a single intramuscular injection of 30 mg vancomycin/kg b.wt. in normal chickens. the maximum serum concentration [Cmax. = 25.03 f 1.14 ug / ml] was recorded at two hours with half-life of absorption equal to [t0.5(ab). = 0.56
± 0.09 h]. The elimination half-life [t0.5 03) was equal to 2.28
± 0.05 hours. The first order transfere rate constant for disappearance of drug from central compartment [ Kei] was equal to 0.31 ± 0.007 h-1. The total body clearance [CLtot.] was 3.81 ± 0.15 ml/kg/min. The mean systemic bioavailability following single intramuscular injection was 43.61 ± 2.44 %. During repeated intramuscular injections of 30 mg vancomycin/kg.b.wt. three times daily for five consecutive days in normal chickens ,the highest serum concentrations of the drug achieved after two hours post each dose. The tissue concentrations of vancomycin, 12 hours after the last dose of repeated intramuscular injections were 67.5 ± 2.17 ug/g in liver, 61.66 ± 4.80 ug/g in kidney, 22.96 ± 2.33 ug/g in lung, 16.33 ± 0.88 ug.g in gizzard, 21.63 1.30 ug/g in heart, 14.8 0.43 ug/g in fat, 16.43 ± 0.74 ug/g in thigh muscle, and 15.63 ± 0.73 ug/g in breast muscle. The drug persisted in liver and kidney for 120 hours the last after administration,vancomycin disappeared from all body tissues 144 hours after the last dose of repeated administration. The in- vitro protein binding percent of
vancomycin was 5.81 ±0.57%. It is concluded that the withdrawal time of netilmicin and vancomycin were five days and six days, respectively to be sure that all tissues were free from the drug residues. and total lipids and a significant increase in the serum ALT and copper levels. While during luteal phase, serum glucose, total lipids, copper and progesterone levels were significantly decreased than control. But serum total cholesterol, ALT, calcium and potassium levels were significantly higher compared with control.
2-In groupIII, synchronized by veramix vaginal sponge, the results
compared with control group were as following: During follicular phase, serum total proteins and globulin levels were significantly decreased. But total lipids, total cholesterol, ALT and calcium were significantly increased. In the mean time during luteal phase serum glucose, AST, ALT and copper were significantly decreased.
3-The ewes synchronized by PGF2a show low fertility at first estrus than second one and some blood parameters, glucose, total proteins, globulin, total lipids, calcium, sodium and progesterone were significantly decreased and serum AST and ALT showed significant increased at first estrus than seconed one.