الفهرس 
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Abstract
The present work was carried out to reveales some pharmacokinetic aspects of tulathromycin alone and concurrently with flunixin meglumine in goats.The bioavailability of tulathromycin following subcutaneousinjectionand the protein binding percent of the drug to serum was also estimated.
The present study was carried out on 10 goats. These animals were obtained from local market inBeni-Suef Governorate with an average body weight from 12.5 to 23 kg and proved to be clinically healthy.
In the first experiment five clinically healthy goats were given tulathromycin 2.5 mg/kg b.wt.as a single intravenious dose (through jugular vein) and single suncutaneous dose with two weeks washout period between each route. The other five goats were injected intravenously with 2.5 mg/kg b.wt. tulathromycin concurrently with 2.2 mg/kg b.wt. flunixin meglumine and after two weeks the same treatment was repeated through subcutaneous injection.
Blood samples were collected 5, 10, 15 and 30 min. 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post injection. The concentration of the drug in serum sample was determined using the microbiological assay method.
III- Administration of a single dose of tulathromycin alone:-
1- Intravenous injection:
After intravenous injection of tulathromycin in a dose of 2.5 mg /kg b.wt. , the drug was showed a high serum level (91.2 ug / ml) 5 min post injection, then the concentration decreased gradually till reached its minimum level (0.27 ug/ ml) at 72 h post –injection. The present data revealed that the serum concentration time curves of tulathromycin were best described by a two compartment –open model.
The drug was rapidly distributed with a distribution half-life (t 0.5 α) of 0.071 h and apparent volume of distribution at steady state Vd(ss)was0.249 l/kg. The drug was distributed in the central compartment with a volume of distribution (Vc) 0.0132 l/kg., indicating that the drug is highly distributed in extra vascular tissues.
The drug was eliminated with a half-life of elimination (t0.5β) of 6.43 and the body clearance of tulathromycin (ClB) was 0.046 l/kg/h. The mean residence time (MRT) was 6.27 h.
2- Subcutaneous injection :
Following subcutaneous administration of tulathromycin in a single dose of 2.5 mg/kgb.wt., the drug was detected in serum 5 min post injection (0.91 ug/ ml) and it continued to increase gradually thereafter and was reached its maximum level 3.7 ug/ml at 0.98 h post injection, then started to decrease gradually till reached its lowest concentration 0.16 ug/ ml at 72 hours. It was rapidly absorbed with a half-life of absorption (t0.5ab) of 0.54 h., while its elimination half-life (t0.5el) was 13.5 h .The systemic bioavailability of tulathromycin following subcutaneous injection was 89.9 %. This indicated good absorption of the drug from this site of injection.
IV- Administration of a single dose of tulathromycin concurrently with single dose flunixin meglumine :-
2- Intravenous injection:
The drug was showed a high serum level (15.33 ug/ml) 5 min. post injection, and then the concentration decreased gradually till reached its minimum level (0.11 ug/ ml) at 72 h post –injection. The present data revealed that the serum concentration time curves of tulathromycin were best described by a two compartment –open model.
The drug was rapidly distributed with a distribution half-life (t0.5 α) of 0.046 h and apparent volume at steady state Vd(ss)was0.96 L/kg respectively. The drug was distributed in the central compartment with a volume of distribution (Vc) 0.061 L/kg., indicating that the drug is highly distributed in extra vascular tissues.The drug was eliminated with a half-life of elimination (t0.5β) of 5.05 and the body clearance of tulathromycin (ClB) was 0.17 l/kg/h. The mean residence time (MRT) was 5.99 h.
3- Subcutaneous injection:
The drug was detected in serum 5 min post injection (0.37 ug ml-1) and it continued to increase gradually thereafter and was reached its maximum level 2.59 ug / mlat 0.95 h post injection, then started to decrease gradually till reached its lowest concentration 0.13 ug/ml at 72 hours. It was rapidly absorbed with a half-life of absorption (t0.5ab) of 0.34 h., while its elimination half-life (t0.5el) was 1.8 h. The systemic bioavailability of tulathromycin following subcutaneous injection concurrently with flunixin meglumine was 205.7 %.
V- In-Vitro protein binding
Tulathromycin was moderately bound to serum protein in goatsat low extent (18.72 %).