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.

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 pharmacokinetics of a diclofenac sodium was investigated in swine. A single intravenous (i.v.) or intramuscular (i.m.) injection of 5% diclofenac sodium (concentration = 2.5 mg · kg-1) was administered to 8 healthy pigs according to a two-period crossover design. The pharmacokinetic parameters were calculated by non-compartmental analysis with DAS2.1.1 software. After a single i.v. administration, the main pharmacokinetic parameters of diclofenac sodium injection in swine were as follows: the elimination half-time (T1/2β) was 1.32±0.34 h; the area under the curve (AUC) was (55.50±5.50 μg · mL-1 h; the mean residence time (MRT) was 1.60±0.28 h; the apparent volume of distribution (Vd) was 0.50±0.05 L · kg-1; and the body clearance (CLB) was 0.26±0.04 L · (h · kg)-1. After the single i.m. administration, the pharmacokinetic parameters were as follows: peak time (Tmax) was 1.19±0.26 h; and peak concentration (Cmax) was 11.61±5.99 μg mL-1. The diclofenac sodium has the following pharmacokinetic characteristics in swine: rapid absorption and elimination; high peak concentration; and bioavailability.

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.

Ibudilast (AV-411) is a non-selective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is currently marketed for human use in Asian countries for the treatment of asthma, cerebrovascular disorders and ocular allergies. Ibudilast has also been found to have an analgesic action for neuropathic pain at doses 5-10 times higher than those used in asthma therapy. Six healthy Labrador dogs were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, cross-over design (2x2 Latin-square). Dogs in group 1 (n=3) were fasted for at least 10 hours overnight before the beginning of the experiment and 4 h following dosing while dogs in group 2 (n=3) received food ad libitum. During the first phase, each dog in group 1 and 2 received a single dose of 5 mg/kg ibudilast administered orally. After 1-week washout period the groups were rotated and the experiment was repeated. The analytical method, validated for dog plasma, was shown to be linear in the range 0.10–20 μg/mL. The limit of detection (LOD) and quantification (LOQ) were 0.03 and 0.1 μg/mL, respectively. No behavioural or health alterations were observed in the animals during or after the study. Ibudilast was detectable in plasma for up to 24 h showing a wide variability between animals. Although no statistically significant differences were observed in the present study between the fed and fasted states, examination of the raw data suggests that an effect may be present. The wide degree of variation observed in area under the curve (AUC) suggests that the investigation of population pharmacokinetic modelling is warranted.

Canine status epilepticus (CSE) is characterized by epileptic seizures that are longer than 5 min or more than one seizure with incomplete recovery. Currently, diazepam suppositories are generally prescribed for CSE. Levetiracetam (LEV) is one of the newest antiepileptic drugs currently available. This study compared the pharmacokinetics of intragastric and intrarectal administration in oral formula of LEV in four healthy beagles as a reference data when the owner administers levetiracetam to dogs by himself at home. Blood for measuring plasma LEV concen- trations was collected 0, 30, 60, 90, 120, 240, 360, and 540 min after LEV administration. The time to reach the maximum plasma concentration (Tmax) was markedly shorter with intra- rectal administration (45±26 min) than with intragastric administration (270±99 min). Intrarectal administration of LEV tablets could be an effective option for treating canine seizures although it might be a limit for treating CSE because the absorption rate is not fast enough.

In the current study, twenty lambs, aged 4 months, half male and half female, were classified into four groups, with five in each group. The experimental three groups of lambs were given intravenous (IV), intramuscular (IM) and subcutaneous (SC) administrations of recombinant ovine interferon-τ (roIFN-τ). The fourth group (normal control) of lambs was given normal saline injections in the same way. After administrations, blood samples were collected from the tested animals at different time points post injection, and the serum titers of roIFN-τ were measured using cytopathic effect (CPE) inhibition bioassay. The results of calculating pharmacokinetic (PK) parameters using DAS software showed that the PK characteristics of roIFN-τ through IV injection conformed to the two-compartment open model, whose half-life of distribution phases (T1/2α) was 0.33±0.034 h and the elimination half-life(T1/2β) was 5.01±0.24 h. However, the PK features of IM injection and SC injection of roIFN-τ conformed to the one compartment open model, whose Tmax were 3.11±0.26 h and 4.83±0.43 h, respectively, together with an elimination half life(T1/2β) of 9.11±0.76 h and 7. 43±0.58 h, and an absorption half-life (T1/2k(a)) of 1.13±0.31 h and 1.85±0.40 h, respectively. The bioavailability of roIFN-τ after IM administration reaches 73.57%, which is greater than that of SC administration (53.43%). These results indicate that the drug administration effect can be preferably obtained following a single dose IM administration of the roIFN-τ aqueous preparation. This study will facilitate the clinical application of roIFN-τ as a potential antiviral agent in future work.

Propofol infusion in anesthesia administration requires continual adjustment in the manual infusion system to regulate the hypnosis level. Hypnotic level is based on Bispectral Index Monitor (BIS) showing the cortical activity of the brain scaled between 0 to 100. The new challenging aspect of automation in anaesthesia is to estimate the concentration of hypnotic drugs in different compartments of the body including primary, rapid peripheral (muscle), slow peripheral (bones, fat) and effect site (brain) compartment based on Pharmacokinetics (PK) and Pharmacodynamics (PD) model. This paper aimed to regulate the hypnosis level with estimating the Propofol concentrations using a linear observer in feedback control strategy based on Integral Super-Twisting Sliding Mode Controller (ISTSMC). The drug concentration in plasma of the silico patients accurately estimated in nominal transient. The results show that tracking errors between the actual output in form of BIS level and linearized output nearly approaches to zero in the maintenance phase of anesthesia to ensure the controller response on sliding phase with optimum performances by achieving desired hypnotic level 50 on BIS. The robustness of control strategy is further ensured by adding measurement noise of electromagnetic environment of operation theatre distracting signal quality index of the output BIS level.