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Abstract The pharmacokinetics of levofloxacin was studied on 15 female lactating goats (10 normal and 5 experimentally Escherichia coli infected goats). Goats were divided into 3 groups each one included 5 goats. The pharmacokinetics and bioavailability levofloxacin were calculated in normal goats after a single intravenous and intramuscular dose. The drug clearance, urine output and retaining clearance were investigated in normal and experimentally Escherichia coli infected goats following intramuscular administrations of 4 mg levofloxacin /kg.b.wt. twice daily for five consecutive days. The in vitro protein binding percent of levofloxacin was determined microbiologically. Following a single intravenous injection of 4 mg levofloxacin /kg.b.wt. in normal goats, levofloxacin could be detected for 12 hours post intravenous dose with value equal to 0.032±0.004 ug/ml. the serum concentration-time curve of levofloxacin following intravenous injection showed that the drug obeyed a two-compartments open model. This observation indicated that the body was viewed as consisting of two - compartments: a central co mpartment of plasma and rapid equilibrating tissues, and a deeper slower equilibrating compartment (skin and connective tissues). Levofloxacin after intravenous dose revealed a rapid distribution phase [α] equal to 4.08 ± 0.06 h-1 with a distribution half-life [t0.5(α)] equal to 0.17 ± 0.003 h. The volume of distribution of levofloxacin to the central compartment [V1 c] was 558.69±28.62 ml/kg., whereas the calculated body distribution by extrapolation [Vd(B)], area [Vd(area)] and steady -state [Vdss] methods were 924.62±15.10, 878.82±17.21 and 854.81±35.65 ml/kg respectively. Levofloxacin was transferred from central to peripheral compartment [K12] at slower rate 1.65 ± 0.05 h-1 than its passage from peripheral to central compartment [K21] equal to 2.46 ± 0.05 h-1. Levofloxacin was eliminated after intravenous injection with a half-life [t0.5(β)] value of 1.53 ± 0.05 h and cleared by all clearance processes in the body at a rate of 3.39 ± 0.06 ml/kg/min. Following a single intramuscular injection o f 4 mg levofloxacin /kg.b.wt. in normal goats, the drug reached its maximum serum concentrations after 1hour of injection with value equal to 3.13 ± 0.03 ug/ml Levofloxacin could be detected for 12 hours post intramuscular dose with value equal to 0.12± 0.006 ug/ml. The absorption half life [t0.5(ab)] was 0.30 ± 0.003 h. Apparent elimination half-life [t0.5(β)] was 2.27 ± 0.06 h and levofloxacin was cleared by all clearance processes [Cltot] with rate equal to 4.82 ± 0.06 ml/kg/min. The mean systemic bioavailability of levofloxacin following a single intramuscular injection in normal goats was 93.38±0.54 %; this value referred a better absorption of levofloxacin from its site of intramuscular administration. The serum concentrations of levofloxacin in normal and experimentally Escherichia coli infected goats following repeated intramuscular injections of 4 mg/kg. b.wt. twice daily for five consecutive days, peaked 1 hour after each intramuscular dose with a lower significant values recorded in experimentally Escherichia coli infected goats than in normal goats. This observation might be attributed to the higher penetrating power of the drug to diseased tissues. The apparent first order absorption rate constants [Kab] are significantly lower in Es c he r ic hia co l i infected goats than in normal goats following 1st, 3rd, 7th and 9th doses. The results illustrated a significant decrease in the maximum serum concentrations [Cmax] in Es c he r ic hia c o li infected goats than in normal goats following all doses., while absorption half lives [t0.5(ab)] are significantly higher in Es c he r ic hia co li infected goats than in normal goats following 1st, 3rd, 7th and 9th doses. The elimination half lives [t0.5(β)] are significantly lower in Es c her ic hia c o li infected goats than in normal goats following all doses. Levofloxacin is cleared by all clearance processes [Cltot] in the body at faster significant rates in Es c he r ic hia co li infected goats than in normal goats. The mean peak urine concentrations of levofloxacin are reached 1. |