Ketoprofen (KTP) and meloxicam (MLX) are non-steroidal anti-inflamatory drugs used extensively in veterinary medicine. The pharmacokinetics of these drugs were studied in eight dogs following a single oral dose of 1 mg/kg of KTP as a racemate or 0.2 mg/kg of MLX. The concentrations of the drugs in plasma were determined by high-performance liquid chromatography (HPLC). There were differences between the disposition curves of the KTP enantiomers, confirming that the pharmacokinetics of KTP is enantioselective. (S)-(+)-KTP was the predominant enantiomer; the S:R ratio in the plasma increased from 2.58 +/- 0.38 at 15 min to 5.72 +/- 2.35 at 1 h. The area under the concentration time curve (AUC) of (S)-(+)-KTP was approximately 6 times greater than that of (R)-(-)-KTP. The mean (+/- SD) pharmacokinetic parameters for (S)-(+)-KTP were characterized as Tmax = 0.76 +/- 0.19 h, Cmax = 2.02 +/- 0.41 microg/ml, t1/2el = 1.65 +/- 0.48 h, AUC = 6.06 +/- 1.16 microg.h/ml, Vd/F = 0.39 +/- 0.07 L/kg, Cl/F = 170 +/- 39 ml/(kg.h). The mean (+/- SD) pharmacokinetic parameters of MLX were Tmax = 8.5 +/- 1.91 h, Cmax = 0.82 +/- 0.29 microg/ml, t1/2lambda(z) = 12.13 +/- 2.15 h, AUCinf = 15.41 +/- 1.24 microg.h/ml, Vd/F = 0.23 +/- 0.03 L/ kg, and Cl/F = 10 +/- 1.4 ml/(kg.h). Our results indicate significant pharmacokinetic differences between MLX and KTP after therapeutic doses.
The pharmacokinetic properties of the fluoroquinolone levofloxacin, were investigated in five cats after single intravenous and repeat oral administration at a daily dose of 10 mg/kg. Levofloxacin serum concentration was analyzed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as test microorganism. Serum levofloxacin disposition after intravenous and oral dosing was best fitted to a bicompartmental and a monocompartmental open models with first-order elimination, respectively. After intravenous administration, distribution was rapid (t(1/2(d)) 0.26 +/- 0.18 h) and wide as reflected by the steady-state volume of distribution of 1.75 +/- 0.42 L/kg. Drug elimination was slow with a total body clearance of 0.14 +/- 0.04 L/h.kg and a t(1/2) for this process of 9.31 +/- 1.63 h. The mean residence time was of 12.99 +/- 2.12 h. After repeat oral administration, absorption half-life was of 0.18 +/- 0.12 h and Tmax of 1.62 +/- 0.84 h. The bioavailability was high (86.27 +/- 43.73%) with a peak plasma concentration at the steady state of 4.70 +/- 0.91 microg/mL. Drug accumulation was not significant after four oral administrations. Estimated efficacy predictors for levofloxacin after either intravenous or oral administration indicate a good profile against bacteria with a MIC value below of 0.5 microg/mL. However, for microorganisms with MIC values of 1 microg/mL it would be efficacious only when administered intravenously.
The pharmacokinetic properties of ciprofloxacin, a second-generation fluoroquinolone, were investigated in six cats after single intravenous and repeat oral administration at a dosage of 10 mg/kg b.i.d. Ciprofloxacin serum concentration was analyzed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as microorganism test. Serum ciprofloxacin disposition was best fitted to a bicompartmental and a monocompartmental open models with first-order elimination after intravenous and oral dosing respectively. After intravenous administration, distribution was rapid (t(1/2(d)), 0.22 +/- 0.23 h) and wide as reflected by the steady-state volume of distribution of 3.85 +/- 1.34 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.64 +/- 0.28 L/h.kg and a t(1/2(el)) of 4.53 +/- 0.74 h. After repeat oral administration, absorption was rapid with a half-life of 0.23 +/- 0.22 h and T(max) of 1.30 +/- 0.67 h. However bioavailability was low (33 +/- 12%), the peak plasma concentration at steady-state was 1.26 +/- 0.67 microg/mL. Drug accumulation was not significant after seven oral administrations. When efficacy predictors were estimated ciprofloxacin showed a good profile against gram-negative bacteria when administered either intravenously or orally, although its efficacy against gram-positive microorganisms is lower.
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