Orange juice is a very rich source of dietary flavanones. The effect of flavanone concentration and solubility of orange beverages on their bioavailability has been studied in a crossover study with 10 healthy volunteers. Five different beverages with different flavanone concentrations were evaluated. Commercial orange juices (29.2-70.3 mg of flavanones/100 mL) were compared with experimental orange beverages in which the flavanone concentration was enhanced (110.2 mg/100 mL). Hesperetin and naringenin glucuronides and sulfates were detected and quantified in plasma and urine. The study shows that the solubility of the flavanones, and particularly that of hesperidin, in the juice is a key factor for the bioavailability as flavanone excretion and the C(max) in plasma correlate well with the soluble flavanone concentration in the juice, whereas it has no correlation with the total flavanone intake. In addition, a large interindividual variation was observed, this being consistent for each individual after the intake of the different beverages, suggesting that flavanone bioavailability is also dependent on the occurrence of specific microbiota that is able to remove the rutinosides from the juice glycosides, which results in aglycones that are then absorbed from the gut.

The single-dose disposition kinetics of orbifloxacin were determined in clinically normal lactating goats (n = 6) after intravenous, subcutaneous, and intramuscular administration of 2.5 mg of orbifloxacin/kg of body weight. Orbifloxacin concentrations were determined by HPLC with fluorescence detection. The concentration-time data were analyzed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution and clearance of orbifloxacin after intravenous administration were 1.13 +/- 0.08 L/kg and 0.40 +/- 0.11 L/h x kg, respectively. Following subcutaneous and intramuscular administration, orbifloxacin achieved maximum plasma concentrations of 1.85 +/- 0.20 and 1.66 +/- 0.14 mg/L at 1.25 +/- 0.22 and 0.87 +/- 0.38 h, respectively. The absolute bioavailabilities after subcutaneous and intramuscular routes were 108.96 +/- 17.61% and 105.01 +/- 15.61%, respectively. Orbifloxacin penetration from the blood into the milk was rapid and showed high levels of concentrations in milk secretion. From this data, orbifloxacin could have success against susceptible mastitis pathogens in goats.

The single-dose disposition kinetics of orbifloxacin were determined in clinically normal rabbits (n=6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg bodyweight. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of orbifloxacin against 30 strains of Staphylococcus aureus from several European countries was performed in order to compute pharmacodynamic surrogate markers. The concentration-time data were analysed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution (V(ss)) and total body clearance (Cl) of orbifloxacin after i.v. administration were estimated to be 1.71+/-0.38 L/kg and 0.91+/-0.20 L/h x kg, respectively. Following s.c. and i.m. administration orbifloxacin achieved maximum plasma concentrations of 2.95+/-0.82 and 3.24+/-1.33 mg/L at 0.67+/-0.20 and 0.65+/-0.12 h, respectively. The absolute bio-availabilities after s.c. and i.m. routes were 110.67+/-11.02% and 109.87+/-8.36%, respectively. Orbifloxacin showed a favourable pharmacokinetic profile in rabbits. However, on account of the low AUC/MIC and C(max)/MIC indices obtained, its use by i.m. and s.c. routes against the S. aureus strains assayed in this study cannot be recommended given the risk of selection of resistant populations.

The pharmacokinetics of moxifloxacin was studied following intravenous (i.v.), intramuscular (i.m.) and oral dose of 5 mg/kg to healthy white New Zealand rabbits (n = 6). Moxifloxacin concentrations were determined by HPLC assay with fluorescence detection. The moxifloxacin plasma concentration vs. time data after i.v. administration could best be described by a two-compartment open model. The disposition of i.m. and orally administered moxifloxacin was best described by a one-compartment model. The plasma moxifloxacin clearance (Cl) for the i.v route was (mean +/- SD) 0.80 +/- 0.02 L/h.kg. The steady-state volume of distribution (Vss) was 1.95 +/- 0.18 L/kg. The terminal half-life (t(1/2lambdaz)) was (mean +/- SD) 1.84 +/- 0.12, 2.09 +/- 0.05 and 2.15 +/- 0.07 h after i.v., i.m. and oral, respectively. Minimal inhibitory concentration (MIC) assays of moxifloxacin against different strains of S. aureus were performed in order to compute pharmacodynamic surrogate markers. From these data, it is concluded that a 5 mg/kg dose moxifloxacin would be effective by i.m. and oral routes in rabbits against bacterial isolates with MIC < or = 0.06 microg/mL and possibly for MIC < or = 0.12 microg/mL, but in the latter case a higher dose would be required.

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