Metal ion-oxytetracycline pharmacokinetic interactions after oral co-administration in broiler chickens.

The influence of the composition of calcium (Ca(2+)), magnesium (Mg(2+)), and iron (Fe(3+)) ions in two concentration levels (low-500 mg/L of CaCl2, 125 mg/L of MgCl2, and 10 mg/L of FeCl3 and high-2,500 mg/L of CaCl2, 625 mg/L of MgCl2, and 50 mg/L of FeCl3) contained in water on the pharmacokinetics (PK) of oxytetracycline (OTC) was determined. OTC hydrochloride was administered at a dose of 25 mg/kg of body weight to broiler chickens divided into four groups of nine birds each, including 3 oral groups (in deionized water -control, in water with low ion concentration, and in water with high ion concentration) and 1 intravenous group. OTC concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry, after which non-compartmental pharmacokinetic analysis was conducted.The absolute bioavailability of OTC in the group of birds exposed to higher ions concentration was reduced (8.68% ± 2.56) as compared to the control (13.71% ± 2.60). Additionally, in this group, decrease in PK parameters such as: area under the concentration-time curve from 0 to infinity (15.36 µg × h/mL ± 4.36), from 0 to t (14.78 µg × h/mL ± 4.37), area under the first moment of curve from 0 to t (107.54 µg × h/mL ± 36.48), and maximum plasma concentration (2.13 µg/mL ± 0.32) were also observed. It is noteworthy, all mentioned parameters demonstrated a downward trend with high correlation coefficient (P = 0.004, P = 0.002, P = 0.005, P = 0.004, P = 0.011, respectively), reflecting the influence of increasing concentrations of Ca(2+), Mg(2+), and Fe(3+) ions on the decreasing absorption rate of OTC.Based on the current research results, it can be assumed that high concentrations of several ions applied concomitantly are able to decrease the absorption of OTC from gastrointestinal tract in broiler chickens. This occurrence might impair the drug's clinical efficacy toward some pathogenic microorganisms. It implies that using OTC on a farm may require administration of higher doses than the routine one when infections are caused by less sensitive pathogens.

A comparison of the efficacy and pharmacokinetics of ivermectin after spring and autumn treatments against Cyathostominae in horses.

The aim of the present study was to determine the efficacy of ivermectin against Cyathostominae infections and to describe the drug's pharmacokinetic parameters during two seasonal deworming treatments in horses. The study was performed on warm-blooded mares aged 3-12 years weighing 450-550 kg. A single bolus of an oral paste formulation of ivermectin was administered at a dose of 0.2 mg/kg BW in spring and autumn. Fecal samples were tested before treatment and 1, 2, 3, 4, 6, 10, 20, 30, 40, 50, 60, 75 days after treatment. Ivermectin concentrations in blood samples collected before treatment, 0.5, 1, 2, 3, 4, 6, 12, 24, 36 and 48 hours after treatment, and 3, 4, 6, 8, 10, 15, 20, 25, 30, 40, 50, 60 and 75 days after drug administration were determined by high pressure liquid chromatography. Drug absorption was significantly (p<0.05) slower (tmax: 21.89±11.43 h) in autumn than in spring (tmax: 9.78±8.97 h). Maximum concentrations (Cmax) of ivermectin in the blood plasma of individual horses (8.40-43.08 ng/ml) were observed 2-24 h after drug administration during the spring treatment and 2-36 h (6.43-24.86 ng/ml) after administration during the autumn treatment. Significantly higher (p<0.05) ivermectin concentrations were found during the first 4 hours after administration in spring in comparison with those determined after the autumn treatment. The administration of the recommended dose of ivermectin resulted in 100% elimination of parasitic eggs from feces in spring and autumn treatment.

Prostaglandin E2 inhibits IL-10 production by bovine CD4+ T cells.

Although prostaglandin E2 (PGE2) is a pro-inflammatory mediator, it also produces some effect which is anti-inflammatory in character. It is suggested that one of the mechanisms responsible for the latter effect is the increased synthesis of IL-10. The aim of this study has been to determine the influence of PGE2 on IL-10 production by bovine CD4+ and CD8+ T cells and NK cells. With this aim, peripheral blood mononuclear cells collected from 12-month-old heifers (n = 10) were treated without or with PGE2 (10(-6) M). Flow cytometric analysis showed that PGE2 caused a reduction in the percentage of IL-10 producing CD4+ T cells (P < 0.001), while leaving the secretion of this cytokine by CD8+ T cells and NK cells unaffected. This seems to indicate that PGE2 in cattle does not produce an anti-inflammatory effect by increasing the synthesis of IL-10; contrary to this, it may aggravate an inflammatory response by inhibiting the secretion of this cytokine by CD4+ T cells.

The influence of doxazosin, an alpha1-adrenergic receptor antagonist on the urinary bladder contractility in pigs.

In the present study influence of doxazosin on the porcine urinary bladder contractility has been examined. Immature pigs were treated for 30 days with: a) doxazosin (n = 5) per os at a dose of 0.1 mg/kg b.w. or b) placebo (n = 5; control group). Thereafter, animals were sacrificed and urinary bladder strips from the trigone were suspended in organ baths. The tension of the smooth musce was measured before and after exposition to acetylocholine (ACh; 10(-5) - 10(-3) M), norepinephrine (NE; 10(-9) - 10(-7) M) and 5-hydroxytryptamine (5-HT; 10(-7) - 10(-5) M). Both the ACh and 5-HT at the highest doses significantly increased the contractility in each group, but this response was weaker in doxazosin-treated animals. NE caused relaxation in both groups, but the effect was weaker in doxazosine-treated group. The results of our study have shown that long-term administration of doxazosin caused a desensitization of the detrusor smooth muscle for in vitro applied mediators of the autonomic nervous systems.

Pharmacological characteristics of metamizole.

Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca2+ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole-induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge.

Pharmacokinetics of orally administered simvastatin in turkeys.

The aim of the present study was to determine the pharmacokinetics of simvastatin (SIM) administered orally in 6-week-old turkeys at a single dose of 2 mg/kg b.w. The SIM concentrations in plasma were determined by validated HPLC-MS/MS method. Mean (+/- SD; n = 10) values of pharmacokinetic parameters evaluated were as follows: Cmax = 0.49 +/- 0.21 ng/ml, t(max) = 1.6 +/- 1.1 h, AUC(0-infinity) = 1.08 +/- 0.57 h x ng/ml, t1/2kel = 2.14 +/-1.3 h and MRT = 3.08 +/- 1.52 h. The results indicate that the SIM is absorbed from the gastrointestinal tract of turkeys; however, achieved plasma level is lower compared to those observed in mammals.

Characteristics of selected second-generation antiepileptic drugs used in dogs.

A significant number of cases of clinical canine epilepsy remain difficult to control in spite of the applied treatment. At the same time, the range of antiepileptic drugs is increasingly wide, which allows efficient treatment. In the present paper we describe the pharmacodynamics and pharmacokinetics of the newer antiepileptic drugs which were licensed after 1990 but are still not widely used in veterinary medicine. The pharmacokinetic profiles of six of these drugs were tested on dogs. The results of experimental studies suggest that second generation antiepileptic drugs may be applied in mono- as well as in poli- treatment of canine epilepsy because of the larger safety margin and more advantageous pharmacokinetic parameters. Knowledge of the drugs' pharmacokinetics allows its proper clinical appliance, which, in turn, gives the chance to improve the efficiency of pharmacotherapy of canine epilepsy.