الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
The pharmacokinetics of difloxacin was studied on 12 female lactating goats (8 healthy and 4 experinmentally Escherichia coli infected goats). Goats were divided into 3 groups each one included 4 goats. The pharmacokinetics and bioavailability of the difloxacin were calculated in healthy goats after a single intramuscular dose. The drug clearance, urine output and retaining clearance were investigated in healthy and experimentally Escherichia coli infected goats following a single and repeated intramuscular administration of 5 mg difloxacin /kg.b.wt. once daily for five consecutive days.
Following a single intravenous injection of 5 mg difloxacin /kg.b.wt. in 4 healthy goats, difloxacin could be detected in a therapeutic concentration 24 hours post intravenous dose with value equal to 0.27 μg/ml. the serum concentration time curve of difloxacin following intravenous injection showed that the drug obayedafirst-order two-compartments open mode. This observation indicated that the body was viewed as consisting of two-compartments: a central compartment of serum and rapid equilibrating tissues, and a deeper slower equilibrating compartment (skin and connective tissues). Difloxacin after intravenous dose revealed a rapid distribution phase (α =3.08 h-1) with a distribution half-life (t0.5(α)) of 0.22 h. The volume of distribution at steady state [V(dss)] methods was 0.73 L/kg respectively. Difloxacin was transferred from central to peripheral compartment [K12] at slower rate (1.63 h-1) than its passage from peripheral to central compartment [K21] (1.27 h-1). Difloxacin was decreased after intravenous injection with a half-life [t0.5(β)] value of 5.65 h and cleared by all clearance processes in the body at a rate of 0.10 L/kg/h.
The mean peak urine concentrations of difloxacin were reached 2 hour post intravenous injection with a value of 108.04 µg/ml. the ratio between the urine to serum concentrations ranged from 7.55 to 24.06. These ratios showed a high penetration of difloxacin from blood to urine.
The highest concentration of difloxacin in milk was recorded 2 hours post intravenous dose with mean value of 1.32 µg/ml. The calculated milk/serum concentration ratio following a single intravenous injection increased from 0.5 to 24 hours. These values showed a high penetration of difloxacin from blood to milk.
Following a single intramuscular injection of 5 mg difloxacin/kg.b.wt. in healthy goats,the drug reached its maximum serum concentrations after 2 hours of injection with value equal to 3.92 µg/ml.difloxacin could be detected in a therapeutic concentration 24 hours post intramuscular dose with value equal to 0.28 µg/ml.The absorption half-life [t0.5(ab)] was 0.46 hours,apparent elimination half-life t0.5(el) was 5.64 h.
The mean peak urine concentrations of difloxacin were reached 2 hours post injection in healthy goats (31.80 µg/ml). The ratio between the urine to serum concentrations ranged from 3.03 to 14.31. These ratios showed a high penetration of difloxacin from blood to urine.
The highest concentration of difloxacin in milk was recorded 2 hours post intramuscular dose with mean value of 0.72 µg/ml. The calculated milk/serum concentration ratio following a single intramuscular injection increased from 0.5 to 24 hours. These values showed a high penetration of difloxacin from blood to milk.
The mean systemic bioavailability of difloxacin following a single intramuscular injection in healthy goats was 86.46 %; this value referred a better absorption of difloxacin from its site of intramuscular administration.
The serum concentrations of difloxacin in healthy and experimentally Escherichia coli infected goats following repeated intramuscular injection of 5 mg/kg.b.wt. once daily for five consecutive days, peaked 2 hours after each intramuscular dose with a lower significant values recorded in experimentally Escherichia coli infected goats than in healthy goats. This observation might be attributed to the higher penetrating power of the drug to diseased tissues. The absorption half-lives [t0.5(ab)] following a single intramuscular injection of difloxacin was significantly higher in experimentally Escherichia coli infected goats than healthy goats. The maximum serum concentration (cmax) was significantly lower in experimentally Escherichia coli infected goats than in healthy goats. These concentrations were reached at maximum time (tmax) which were significantly higher in experimentally Escherichiacoliinfected goats than in healthy goats. The elimination half-lives [t0.5(β)] of difloxacin were significantly higher in experimentally Escherichia coli infected goats than in healthy goats.
The mean peak urine concentrations of difloxacin were reached 2 hours after each intramuscular dose with significant lower values in experimentally Escherichia coli infected goats than in healthy goats. This observation might be attributed to the higher penetrating power of the drug to the diseased tissues.
The highest concentrations of difloxacin in milk reached 2 hours after each intramuscular dose with significantlower values in experimentally Escherichia coli infected goats than inhealthy goats. These observations might be attributed to accumulation of drug in inflamed tissues. The experimental milk/serum concentration ratios of difloxacin showed a high penetration of difloxacin from blood to milk. The high penetration of difloxacin from blood to milk might be attributed to its high oil water partition co-efficient and considerable low binding to serum protein.