Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration in Shetland ponies sedated with xylazine

The pharmacokinetics of ketamine and norketamine enantiomers after administration of intravenous (IV) racemic ketamine (R-/S-ketamine; 2.2 mg/kg) or S-ketamine (1.1 mg/kg) to five ponies sedated with IV xylazine (1.1mg/kg) were compared. The time intervals to assume sternal and standing positions were recorded. Arterial blood samples were collected before and 1, 2, 4, 6, 8 and 13 min after ketamine administration. Arterial blood gases were evaluated 5 min after ketamine injection. Plasma concentrations of ketamine and norketamine enantiomers were determined by capillary electrophoresis and were evaluated by non-linear least square regression analysis applying a monocompartmental model. The first-order elimination rate constant was significantly higher and elimination half-life and mean residence time were lower for S-ketamine after S-ketamine compared to R-/S-ketamine administration. The maximum concentration of S-norketamine was higher after S-ketamine administration. Time to standing position was significantly diminished after S-ketamine compared to R-/S-ketamine. Blood gases showed low-degree hypoxaemia and hypercarbia.     

Effects of topical 0.5% levobunolol alone or in association with 2% dorzolamide compared with a fixed combination of 0.5% timolol and 2% dorzolamide on intraocular pressure and heart rate in dogs without glaucoma

The goal of glaucoma management is to reduce intraocular pressure (IOP) and maintain it at a level compatible with the health of the optic nerve. New therapies are constantly being sought. Topical instillation of levobunolol 0.5%, alone or with dorzolamide 2%, has a hypotensive effect on the IOP in healthy dogs, and levobunolol combined with dorzolamide produces a stronger hypotensive effect than the combination of timolol and dorzolamide. All animals tolerate these topical medications well with no signs of discomfort, and no ocular side effects have been observed. Levobunolol, alone or in combination with dorzolamide, induces bradycardia, as does timolol with dorzolamide.     

The evaluation of non-specific immune status of heifers in field conditions during the periparturient period

During the periparturient period, some impairment of immune defences were observed. Reference values for the different non-specific immune parameters in cows are not generally available, thus limiting the application of these parameters in dairy practice. This paper reports the data on the measurements of different parameters in the blood, and explores the possible influence of the herd on the non-specific immune status of the cow. Five herds located in Northern Italy were selected and overall 39 heifers were enrolled in the trial. Blood samples were taken 14 and 7 days before the expected date of calving, then at 7, 14, 21, 28, 45, 60, and 75 days after calving. The parameters assessed were N-acetyl-beta-glucosaminidase (NAGase), lysozyme, nitric oxide, superoxide dismutase, haptoglobin, respiratory burst, and serum protein profile. After calving, a significant decrease of respiratory burst and nitric oxide concentration were observed in comparison with the pre-calving values but not with the post-calving samplings. Total proteins, beta- and gamma-globulins showed a progressive and significant increase in concentration after calving, in comparison with pre-calving values. The results of the study confirmed that a decrease of immune functions can be observed in commercial dairy herds in the first four weeks after calving. The amplitude of this phenomenon is not common to all animals and all herds, suggesting the possibility to reduce the impairment by improved management and genetic selection.     

Influence of marbofloxacin on the pharmacokinetics and pharmacodynamics of tolfenamic acid in calves

Pharmacokinetic and pharmacodynamic properties of tolfenamic acid (TA) in calves were determined in serum and fluids of inflamed (carrageenan administered) and non-inflamed subcutaneously implanted tissue cages after intramuscular administration both alone and in combination with marbofloxacin (MB). MB significantly altered the pharmacokinetics of TA: mean values were Cmax = 2.14 and 1.64 microg/mL, AUC = 27.38 and 16.80 microg.h/mL, Vd(area)/F = 0.87 and 1.17 L/kg, and ClB/F = 0.074 and 0.128 L/kg/h, respectively, after administration of TA alone and TA + MB. T(1/2)K10 and MRT were not significantly different for the two treatments. The pharmacodynamic properties of TA were not influenced by MB co-administration, in spite of the alterations in some TA pharmacokinetic parameters. TA inhibited prostaglandin E2 (PGE2) synthesis in vivo in inflammatory exudate by 50-88% for up to 48 h after both TA treatments. Inhibition of synthesis of serum thromboxane B2 (TxB2) ex vivo ranged from 40 to 85% up to 24 h after both TA and TA + MB. From the derived pharmacokinetic and eicosanoid inhibition data for TA, pharmacodynamic parameters for serum TxB2 and exudate PGE2 inhibition expressing efficacy (Emax = 78.1 and 97.5%), potency (IC50 = 0.256 and 0.265 microg/mL), sensitivity (N = 1.96 and 2.29) and the pharmacokinetic parameter equilibration time (t(1/2)K(e0) = 0.695 and 24.0 h), respectively, were determined. In this model TA was a nonselective inhibitor of cyclo-oxygenase (COX) (COX-1:COX-2 IC50 ratio = 1.37). TA, both alone and co-administered with MB, did not affect leucocyte numbers in exudate, transudate or blood. Partial attenuation of skin temperature rise over inflamed tissue cages and reduction of zymosan-induced skin swelling were recorded after administration of TA and TA + MB with no significant differences between the two treatments. These data provide a basis for the rational use of TA in combination with MB in calf medicine.     

Prevalence of Demodex canis‐positive healthy dogs at trichoscopic examination

Demodex canis is thought to be present in small numbers in the skin of most healthy dogs; however, available data on the prevalence of normal dogs harbouring D. canis are scarce. The purpose of this study was to investigate, using microscopic examination of plucked hairs, the prevalence of healthy dogs harbouring D. canis. Seventy‐eight clinically healthy dogs with no history of dermatological problems and clinically normal skin and hair coat were included in the study. Five areas (perioral skin 2–3mm from both labial commissures, periungual skin of the third digit of both anterior paws and chin) were examined in each dog. Fifty to sixty hairs were plucked from each skin site and microscopically examined. No D. canis mites were observed and only one adult form of Demodex injai was found in the labial commissure of one dog. Based on these results, the estimated prevalence of healthy dogs harbouring D. canis in clinically normal skin should not exceed the threshold of 5.4%, with 95% confidence level. Considering our and previous findings, we propose that, although small numbers of D. canis might inhabit the skin of normal dogs, the probability of finding these mites in normal dogs is low. Consequently, in most cases, the presence of a D. canis mite in the skin should not be considered as indicative of normality.     

Pharmacodynamics,chiral pharmacokinetics and PK-PD modelling of ketoprofen in the goat

There have been few studies of the pharmacodynamics of nonsteroidal antiinflammatory drugs (NSAIDs) using PK-PD modelling, yet this approach offers the advantage of defining the whole concentration-effect relationship, as well as its time course and sensitivity. In this study, ketoprofen (KTP) was administered intravenously to goats as the racemate (3.0 mg/kg total dose) and as the single enantiomers, S(+) KTP and R(-) KTP (1.5 mg/kg of each). The pharmacokinetics and pharmacodynamics of KTP were investigated using a tissue cage model of acute inflammation. The pharmacokinetics of both KTP enantiomers was characterized by rapid clearance, short mean residence time (MRT) and low volume of distribution. The penetration of R(-) KTP into inflamed (exudate) and noninflamed (transudate) tissue cage fluids was delayed but area under the curve values were only slightly less than those in plasma, whereas MRT was much longer. The S(+) enantiomer of KTP penetrated less readily into exudate and transudate. Unidirectional inversion of R(-) to S(+) KTP occurred. Both rac-KTP and the separate enantiomers produced marked inhibition of serum thromboxane B2 (TxB2) synthesis (ex vivo) and moderate inhibition of exudate prostaglandin E2 (PGE2) synthesis (in vivo); pharmacodynamic variables for S(+) KTP were Emax (%) = 94 and 100; IC50 (microg/mL) = 0.0033 and 0.0030; N = 0.45 and 0.58, respectively, where Emax is the maximal effect, IC50 the plasma drug concentration producing 50% of Emax and N the slope of log concentration/effect relationship. The IC50 ratio, serum TxB2:exudate PGE2 was 1.10. Neither rac-KTP nor the individual enantiomers suppressed skin temperature rise at, or leucocyte infiltration into, the site of acute inflammation. These data illustrate for KTP shallow concentration-response relationships, probable nonselectivity of KTP for cyclooxygenase (COX)-1 and COX-2 inhibition and lack of measurable effect on components of inflammation.     

Physical and nutritional properties of buffalo meat finished on hay or maize silage‐based diets

The current study examines the effect of different finishing diets (hay‐ vs. maize‐silage on meal ration) on carcass quality, physical, chemical and sensory properties, and fatty acid profiles of buffalo meat. Twenty male Italian Mediterranean buffaloes (246 ± 9.00 kg live weight) were distributed at random into two groups at the beginning of the finishing period (368 ± 20 days). The buffaloes were offered two finishing diets: a maize silage (MS) or an alfalfa hay (AH) diet. No significant differences were found between dietary treatments for live and carcass weight. Meat chemical composition was influenced by dietary treatment. A higher fat content was detected in meat from animals finished with MS than AH (P < 0.05). Overall, the data indicated differences between the fatty acid profiles of meat as a consequence of different feeding systems. The higher fat deposition in the MS group resulted in meat with a less favorable fatty acid profile (i.e. a lower polyunsaturated/saturated fatty acid ratio and α‐linolenic fatty acid content) in relation to human health compared with meat from animals fed the AH diet.