Hard water may increase the inhibitory effect of feed on the oral bioavailability of oxytetracycline in broiler chickens.

The aim of this study was to determine to what extent the ions present in hard water (125 mg/L of MgCl2 and 500 mg/L of CaCl2) may intensify the feed-induced decrease in oxytetracycline (OTC) absorption rate in broiler chickens after single oral administration at a dose of 15 mg/kg. Drug concentrations in plasma were determined by liquid chromatography-tandem mass spectrometry and combined, compartmental and non-compartmental approach was used to assess OTC pharmacokinetics. The administration of feed decreased the absolute bioavailability (F) of OTC from 12.70%±4.01 to 6.40%±1.08, and this effect was more pronounced after the combined administration of OTC with feed and hard water (5.31%±0.90). A decrease in the area under the concentration- time curve (AUC0-t), (from 10.18±3.24 µg·h/ml in control to 5.13 µg·h/ml±1.26 for feed and 4.26 µg·h/ml±1.10 for feed and hard water) and the maximum plasma concentration of OTC (Cmax) (from 1.22±0.18 µg/ml in control, to 1.01 µg/ml ±0.10 for hard water, 0.68 µg/ml±0.10 for feed and 0.61 µg/ml±0.10 for feed and hard water) was observed. The results of this study indicate that feed strongly decreases F, AUC0-t and Cmax of orally administered OTC. The ions present in hard water increase this inhibitory effect, which suggests that, therapy with OTC may require taking into account local water quality and dose modification, particularly when dealing with outbreaks caused by less sensitive microorganisms.

Differences in the pharmacokinetics of flumequine after single and continuous oral administration in non-fasted broiler chickens.

The aim of this study was to determine the influence of feed on the pharmacokinetics of flumequine (FLU) administered to broiler chickens as follows: directly into the crop (10 mg/kg of BW) of fasted (group I/control) and non-fasted chickens (group II), or administered continu- ously with drinking water (1 g/L for 72 h) and with unlimited access to feed (group III). Plasma concentration of FLU was determined by high-performance liquid chromatography with fluo- rescence detection. In group II, a significant decrease in the maximum concentration (Cmax = 2.13±0.7 µg/mL) and the area under the concentration curve from zero to infinity (AUC0→∞ = 7.47±2.41 µg·h/mL) was noted as compared to the control group (Cmax = 4.11±1.68 µg/mL and AUC0→∞ = 18.17±6.85 µg·h/mL, respectively). In group III, the decrease in AUC was signifi- cant only in the first 3 hours (AUC0→3 = 5.02±1.34 µg·h/mL) as compared to the control group (AUC0→3 = 7.79±3.29 µg·h/mL). The results indicate that feed reduced the bioavailability of FLU from the gastrointestinal tract by at least 50% after the administration of a single oral dose. However, continuous administration of FLU with drinking water could compensate for the feed-induced decrease in absorption after single oral dose.

Influence of leukotriene receptor antagonist on contractile activity of the porcine uterine smooth muscle in the luteal phase and in early pregnancy.

This study analysed the influence of montelukast (MON; 10-8 - 10-4 M), a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist, on the contractility of the porcine uterine smooth muscle in the luteal phase of the oesterous cycle (n=8) and in early pregnancy (n=8). Stimulation of uterine strips in the luteal phase with MON has been shown to significantly reduce the amplitude of con- tractions, but not to affect the tension or frequency of contractions. A statistically significant tension increase and decrease in the frequency and amplitude of contractions was observed in pigs in early pregnancy. This suggests that MON has a different effect on the parameters under study in cyclic and pregnant pigs.