The aim of the research was an examination of potential impact of milk yield on the intercompartmental clearance – distribution clearance as well as determination of the variability of obtained pharmacokinetic parameters by the population approach using a two-compartmental structural model. Blood perfusion has a considerable impact on physiology of the udder and kinetics of drugs that are distributed in this organ. The research was performed on healthy Holstein- Friesian and Polish Black-White cows at the age of 4-10 years. Determination of antibiotics (ampicillin, amoxicillin, cefoperazone, penicillin G prokaine, cloxacillin, cefacetril) concentration was carried out after their every intramammary administration to one quarter of the udder. A population pharmacokinetic model was created to fit milk concentration data. General milk yield of a single cow was used as a variable. A population analysis was conducted using non-linear mixed-effect modeling. The impact of milk productivity was set solely by reference to intercompartmental clearance only in case of penicillin G, cloxacillin and ampicillin. It, has been found that milk yield, depending on a drug, influenced the distribution clearance of the drug to varying degrees. It means indirectly that increased perfusion of the udder has a different impact on drug distribution from the udder to the bloodstream.

From the regulatory point of view a strong link between an animal model and human pharmacodynamics of biological drugs is very important to qualify the model as “relevant”. Consistent changes in cell population between human physiology and animal model gain value of this model which then can be pharmacodynamically “relevant” from the regulatory point of view. Consequently, the aim of this study was to determine how similar to human observations is the effect of selected biological drugs on blood cells in a pig model. The study was to carry out a comparative analysis of the variability of selected biochemical and hematological parameters of the blood after administration of five different human therapeutic monoclonal antibodies (mAbs) after a single subcutaneous (SC) dose in breeding pigs. The tested drugs were siltuximab (Syl- vant®), omalizumab (Xolair®), infliximab (Inflectra®), pembrolizumab (Keytruda®), and vedoli- zumab (Entyvio®) given in a single 1 mg/kg SC injection. Each of the tested drugs exerted a sig- nificant effect on at least two of the tested parameters three weeks after the administration. Siltuximab significantly influenced 9 of the analyzed parameters. Vedolizumab significantly influenced 8 of the analyzed parameters. Infliximab had the lowest impact of all the tested drugs, as it significantly influenced only two of the analyzed parameters. The study has proved that the impact of mAbs on the analyzed parameters can be significantly extended over time. This requires the monitoring of hematological parameters in the pig model even many weeks af- ter administration of a drug in a relatively small dose.

This paper describes a design process of HALE PW-114 sensor-craft, developed for high altitude (20 km) long endurance (40 h) surveillance missions. Designed as a blended wing (BW) configuration, to be made of metal and composite materials. Wing control surfaces provide longitudinal balance. Fin in the rear fuselage section together with wingtips provide directional stability. Airplane is equipped with retractable landing gear with controlled front leg that allows operations from conventional airfields. According to the initial requirements it is twin engine configuration, typical payload consists of electro-optical/infra-red FLIR, big SAR (synthetic aperture radar) and SATCOM antenna required for the longest range. Tailless architecture was based on both Horten and Northrop design experience. Global Hawk was considered as a reference point – it was assumed that BW design has to possess efficiency, relative payload and other characteristics at least the same or even better than that of Global Hawk. FLIR, SAR and SATCOM containers were optimised for best visibility. All payload systems are put into separate modular containers of easy access and quickly to exchange, so this architecture can be consider as a „modular”. An optimisation process started immediately when the so-called “zero configuration”, called PW-111 was ready. It was designed in the canard configuration. A canard was abandoned in HALE PW-113. Instead, new, larger outer wing was designed with smaller taper ratio. New configuration analysis revealed satisfactory longitudinal stability. Calculations suggested better lateral qualities for negative dihedral. These modifications, leading to aerodynamic improvement, gave HALE PW-114 as a result. The design process was an interdisciplinary approach, and included a selection of thick laminar wing section, aerodynamic optimisation of swept wing, stability analysis, weight balance, structural and flutter analysis, many on-board redundant systems, reliability and maintability analysis, safety improvement, cost and performance optimisation. Presented paper focuses mainly on aerodynamics, wing design, longitudinal control and safety issues. This activity is supported by European Union within V FR, in the area Aeronautics and Space.

To date, only a few studies on the azithromycin (AZM) pharmacokinetics in ornamental birds have been published. In the current study AZM concentrations in domestic pigeon (Columba livia domestica) plasma samples were analyzed using a validated ultra-high performance liquid chromatography tandem mass spectrometry method. The aim of the current study was to carry out an analysis of the pharmacokinetics and pharmacodynamics after administration of a single oral dose of a sustained-release AZM formulation and to conduct a simulation of treatment based on selected minimal inhibitory values. The study was performed with 12 healthy adult pigeons, both sexes. The pigeons tolerated AZM very well and no adverse effects were observed in any animal during the study. Based on the observed characteristics of the pharmacokinetics/ /pharmaco dynamics profiles of AZM in pigeons, it should be noted that 35 mg/kg per os as a single starting dose and 25 mg/kg every 24 h are recommended for treatment of both suscep- tible and less susceptible pathogens.

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.