The pharmacokinetics of intravenous fenoldopam in healthy,awake cats

Fenoldopam is a selective dopamine‐1 receptor agonist that improves diuresis by increasing renal blood flow and perfusion and causing peripheral vasodilation. Fenoldopam has been shown to induce diuresis and be well‐tolerated in healthy cats. It is used clinically in cats with oliguric kidney injury at doses extrapolated from human medicine and canine studies. The pharmacokinetics in healthy beagle dogs has been reported; however, pharmacokinetic data in cats are lacking. The goal of this study was to determine pharmacokinetic data for healthy, awake cats receiving an infusion of fenoldopam. Six healthy, awake, client‐owned cats aged 2–6 years old received a 120‐min constant rate infusion of fenoldopam at 0.8 μg/kg/min followed by a 20‐min washout period. Ascorbate stabilized plasma samples were collected during and after the infusion for the measurement of fenoldopam concentration by HPLC with mass spectrometry detection. This study showed that the geometric mean of the volume of distribution, clearance, and half‐life (198 mL/kg, 46 mL/kg/min, and 3.0 mins) is similar to pharmacokinetic parameters for humans. No adverse events were noted. Fenoldopam at a constant rate infusion of 0.8 μg/kg per min was well tolerated in healthy cats. Based on the results, further evaluation of fenoldopam in cats with kidney disease is recommended.     

Serum,milk, and tissue monensin concentrations in cattle with adequate and potentially toxic dietary levels of monensin: pharmacokinetics and diagnostic interpretation

Used in both beef cattle and dairy cows, monensin can provide many health benefits but can, when unintended overexposures occur, result in adverse effects. Information on serum and tissue concentrations following overexposure and/or overt toxicosis which may aid in diagnostics and clinical outcome is lacking. The aim of this study was to determine concentrations of monensin in biological specimens following oral exposure for 10 days to an approved dose (1 mg/kg) and a higher dose (5 mg/kg) of monensin given daily on a body weight basis to 10 dairy cows. No deaths were reported; cows receiving 5 mg/kg showed early signs of toxicosis including depression, decreased feed intake, and diarrhea after 4 days of exposure. Histopathological findings were minimal in most cows. Pharmacokinetic modeling of the detected serum concentrations for the 1 and 5 mg/kg dose groups determined the C_max, T_max, and t_1/2λ to be 0.87 and 1.68 ng/mL, 2.0 and 1.0 h, and 1.76 and 2.32 days, respectively. Mixed regression models showed that the dose level and days since last dose were significantly associated with monensin concentrations in all four tissues, and with cardiac troponin levels. The high dose resulted in a significant elevation of monensin in tissues at approximately 4.7 times compared to the monensin concentrations in the tissues of animals from the low‐dose group. The cTnI concentrations in the high‐dose group were 2.1 times that of cTnI in the low‐dose group. Thus, the ability to diagnose monensin overexposure and/or toxicosis will improve from knowledge of biological monensin concentrations from this study.     

Nanoemulsion formulation of florfenicol improves bioavailability in pigs

Nanotechnology applications in medicine have seen a tremendous growth in the past decade and are being employed to enhance the stability and bioavailability of lipophilic substances, such as florfenicol. This study aimed to examine the pharmacokinetic properties of the formulated oil‐in‐water florfenicol‐loaded nanoemulsion (FF‐NE). FF‐NE and florfenicol control (Nuflor^®) were administered to the pigs at a dose of 20 mg/kg. Nanoemulsion formulation of florfenicol was highly influenced in vivo plasma profile. The in vivo absorption study in pigs indicated that C_max (14.54 μg/mL) was significantly higher in FF‐NE, 3.42 times higher than the marketed formulation. In comparison with the control group, the relative bioavailability of formulated nanoemulsion was up to 134.5%. Assessment of bioequivalence using log‐transformed data showed that the 90% confidence intervals (90% CI) of C_max and AUC_0–∞ were 2.48–4.60 and 1.21–1.72, respectively.     

Pharmacokinetics of methocarbamol and phenylbutazone in exercised Thoroughbred horses

Methocarbamol (MCBL) is commonly used in performance horses for the treatment of skeletal muscle disorders. Current regulatory recommendations for show horses and racehorses are based on a single oral dose of 5 g, although doses in excess of this are often administered. The goal of the current study was to characterize the disposition of MCBL following higher dose administration and administration in combination with another commonly used drug in performance horses, phenylbutazone (PBZ). Exercised Thoroughbred horses were administered various doses of MCBL as a sole agent and MCBL in combination with PBZ. Blood samples were collected at various times, concentrations of MCBL and PBZ measured using LC‐MS/MS and pharmacokinetic parameters calculated using compartmental analysis. Following administration of 15 g of MCBL, either as part of a single‐ or multiple‐dose regimen, a number of horses exceeded the Association of Racing Commissioners International and the United States Equestrian Federation's recommended regulatory threshold at the recommended withdrawal time. There was not a significant difference between horses that received only MCBL and those that received MCBL and PBZ. Results of the current study support an extended withdrawal guideline when doses in excess of 5 g are administered.     

The screening and evaluation of herbs and identification of herbal combinations with anti-viral effects on Newcastle disease virus

1. A total of 25 “heat-clearing and detoxifying” herbs used in Chinese medicine were investigated for their cytopathic effects on the growth of Newcastle Disease virus (NDV) in a chicken fibroblast cell line.

2. The 5 herbs with the highest virus inhibitory effects were Herba agastaches, Flos chrysanthemi indici, Rhizoma anemarrhenae, Astragalus root and Baikal skullcap root and these were used in herbal formulations. Anti-NDV activities of 4 formulations were tested on the growth of NDV in the DF-1 fibroblast cell line.

3. Formulation II, containing Baikal skullcap root, Astragalus root, Anemarrhena rhizome (1:1:2) and formulation IV containing Anemarrhena rhizome, Astragalus root and Flos chrysanthemi indici (1:1:1), which had strong anti-NDV activity in vitro, were used to determine the in vivo inhibitory effects of NDV-infection in chickens. After treatment with the two formulations serum IgY titres against NDV were improved, and morbidity was reduced in the NDV-infected chickens.

4. The results suggest that the components in formulations II and IV acted synergistically to improve resistance to Newcastle disease and provide a basis for the developing an anti-NDV herbal medicine.

     

Early and 24 h post-mortem changes in breast muscle quality traits of two turkey genotypes and their reciprocal crosses raised under semi-confined conditions

1. An experiment was conducted to determine the effect of reciprocal crossing of turkeys on early and 24 h post-mortem changes in quality traits of their breast muscles.

2. The turkeys of slow-growing (SG) and fast-growing (FG) lines as well as SF (SG × FG) and FS crosses (FG × SG) were reared with access to free range.

3. After slaughter turkey breast muscles were examined in the following terms: 5 min, 45 min, 2 h and 24 h post-mortem, for: temperature, pH, glycogen content (G), lactate content (L) and electrical conductivity (EC). Quality attributes of the breast meat were evaluated based on chemical composition, water holding capacity (WHC), cooking loss (%), shear force (N) and colour (L*, a*, b*).

4. Despite differences in the rate of post-mortem changes, the genotype of turkeys had no significant effect upon many quality traits assessed 24 h post-mortem. Meat of lighter birds (SG and SF) was characterised by a lower fat content but a similar protein content compared to meat of FS and FG turkeys. In addition, meat of males from these groups was darker. Meat from the breast muscles of heavier birds (FS and FG) was harder.

5. Significant negative maternal effects were determined for temperature of meat of both male and female turkeys, for pH₂ and EC₂₄ of males as well as for L₂, L₂₄ and cooking loss of female meat. Positive heterosis was confirmed only for pH₂ of female meat and for G₂ of male meat.

6. In summary, the direction of fast- and slow-growing turkey crossing may affect the quality of their meat. However, meat of both types of hybrids reared under semi-confined conditions (with the possibility of using free range) was characterised by appropriate quality parameters.

     

Diffuse idiopathic skeletal hyperostosis of the spine in a nine‐year‐old cat

A nine‐year‐old intact female domestic shorthair cat was evaluated for paraparesis, ataxia and severe spinal hyperaesthesia. Neurological examination indicated a T3‐L3 spinal cord segment lesion. Computed tomography of the thoracolumbar and lumbosacral vertebral column was performed. This showed contiguous smooth new bone formation ventral and lateral to the vertebrae extending from the cranial thoracic area to the lumbosacral junction and appearing similar to canine diffuse idiopathic skeletal hyperostosis. There was also marked dorsolateral stenosis of the vertebral canal at the level of T4‐T5 because of degenerative changes of the facet joints. To the authors’ knowledge, this is the first published report of feline diffuse idiopathic skeletal hyperostosis.     

HSP90 gene expression induced by aspirin is associated with damage remission in a chicken myocardial cell culture exposed to heat stress

1. To understand the potential protection of heat shock protein 90 (HSP90) induced by aspirin against heat stress damage in chicken myocardial cells, enzyme activities related to stress damage, cytopathological changes, the expression and distribution of HSP90, and HSP90 mRNA levels in the myocardial cells exposed to heat stress (42°C) for different durations with or without aspirin administration (1 mg/ml, 2 h prior) in vitro were investigated.

2. Significant increase of enzyme levels in the supernatant of heat-stressed myocardial cells and cellular lesions characterised by acute degeneration, karyopyknosis and karyorrhexis were observed, compared to non-treated cells. However, the lesions of cells treated with aspirin were milder, characterised by earlier recovery of enzyme levels to the control levels and no obvious heat stress-related cellular necrosis.

3. Stronger positive signals in the cytoplasm and longer retention of HSP90 signal in nuclei were observed in aspirin-treated myocardial cells than those of only heat-stressed cells. HSP90 level in the aspirin-treated myocardial cells was 11.1-fold higher than that in non-treated cells, and remained at a high level at the early stage of heat stress, whereas it was just 4.1-fold higher in only heat-stressed cells and returned rapidly to a low level.

4. Overexpression of HSP90 mRNA in aspirin-treated cells was observed throughout the experiment, whereas HSP90 mRNA decreased significantly only in heat-stressed cells.

5. The early higher HSP90 expression induced by aspirin during heat stress was accompanied by decreased heat stress damage, suggesting that aspirin might play an important role in preventing myocardial cells from heat stress damage in vitro.