Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats     

D Rodrigo-Mocholí  E Escudero  E Belda  FG Laredo  V Hernandis 《New Zealand veterinary journal》2018,66(4):172-177

AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats.

METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two–treatment, two-period study. Alfaxalone at a dose of 5?mg/kg was administered either I/V or I/M. Blood samples were collected between 2–480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5–120 minutes after drug administration using a numerical rating scale (from 0–18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded.

RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5–15 minutes after I/V administration and deep sedation (scores 11–15) at 20 and 30 minutes. Deep sedation was observed from 10–45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery.

CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.  相似文献   

Effects of p.o. administered xylitol in cats          下载免费PDF全文

Á. Jerzsele  Z. Karancsi  E. Pászti‐Gere  Á. Sterczer  A. Bersényi  K. Fodor  D. Szabó  P. Vajdovich 《Journal of veterinary pharmacology and therapeutics》2018,41(3):409-414

Xylitol is commonly used as sugar substitute in households. While it has numerous beneficial effects on human health, it is highly toxic to dogs. The goal of this study was to examine whether xylitol has similar deleterious effects, such as hypoglycaemia and acute hepatic failure, on cats. Our research included six healthy middle‐aged cats. Xylitol was dissolved in deionized water and administered p.o. at three doses (100, 500 and 1,000 mg/kg body weight). These dosages have been considered toxic and can cause liver failure or even death in dogs. After every xylitol administration, the basic health status and the blood glucose of cats were observed regularly. Additionally, prior to and 6, 24 and 72 hr after xylitol administration, blood samples were taken to check complete blood count, clinical biochemical parameters and enzymes such as ALT, ALKP, GGT, GLDH, bile acids, BUN, creatinine, phosphate, total protein, albumin, sodium and potassium. There were no significant changes (p > .05) in any of the haematological or biochemical parameters. Blood glucose concentrations did not show any significant alterations, except at 1,000 mg/kg dose, where a mild but significant increase was observed, but it was in physiological range. Based on our results, xylitol did not induce toxic effects on cats.  相似文献   

Bioavailability of suppository acetaminophen in healthy and hospitalized ill dogs          下载免费PDF全文

E. R. Sikina  J. F. Bach  Z. Lin  R. Gehring  B. KuKanich 《Journal of veterinary pharmacology and therapeutics》2018,41(5):652-658

To determine the plasma pharmacokinetics of suppository acetaminophen (APAP) in healthy dogs and clinically ill dogs. This prospective study used six healthy client‐owned and 20 clinically ill hospitalized dogs. The healthy dogs were randomized by coin flip to receive APAP orally or as a suppository in crossover study design. Blood samples were collected up to 10 hr after APAP dosing. The hospitalized dogs were administered APAP as a suppository, and blood collected at 2 and 6 hr after dosing. Plasma samples were analyzed by ultra‐performance liquid chromatography with triple quadrupole mass spectrometry. In healthy dogs, oral APAP maximal concentration (C_MAX=2.69 μg/ml) was reached quickly (T_MAX=1.04 hr) and eliminated rapidly (T1/2 = 1.81 hr). Suppository APAP was rapidly, but variably absorbed (C_MAX=0.52 μg/ml T_MAX=0.67 hr) and eliminated (T_1/2 = 3.21 hr). The relative (to oral) fraction of the suppository dose absorbed was 30% (range <1%–67%). In hospitalized ill dogs, the suppository APAP mean plasma concentration at 2 hr and 6 hr was 1.317 μg/ml and 0.283 μg/ml. Nonlinear mixed‐effects modeling did not identify significant covariates affecting variability and was similar to noncompartmental results. Results supported that oral and suppository acetaminophen in healthy and clinical dogs did not reach or sustain concentrations associated with efficacy. Further studies performed on different doses are needed.  相似文献   

Pharmacokinetics of cefquinome in healthy and Pasteurella multocida‐infected rabbits          下载免费PDF全文

S. T. Elazab  D. E. Schrunk  R. W. Griffith  S. M. Ensley  G. Dell'Anna  K. Mullin  M. G. Elsayed  M. S. Amer  S. M. El‐Nabtity  W. H. Hsu 《Journal of veterinary pharmacology and therapeutics》2018,41(3):374-377

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.  相似文献   

Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows          下载免费PDF全文

M. D. Kleinhenz  P. J. Gorden  J. S. Smith  J. A. Schleining  K. E. Kleinhenz  L. L. Wulf  P. K. Sidhu  D. Rea  J. F. Coetzee 《Journal of veterinary pharmacology and therapeutics》2018,41(3):490-493

A transdermal formulation of the nonsteroidal anti‐inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single‐dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high‐pressure liquid chromatography with mass spectroscopy (HPLC ‐MS ). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software. The time to maximum drug concentration (T max) was 2.81 hr, and the maximum drug concentration was 1.08 μg/ml. The mean terminal half‐life (T½) was determined to be 5.20 hr. Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg^?1, and volume of distribution of fraction (V z/F ) absorbed was 2.20 L/kg. The mean accumulation factor was 1.10 after three doses. This indicates changes in dosing may not be required when giving multiple doses of flunixin transdermal. Further work is required to investigate the clinical efficacy of transdermal flunixin after multiple daily doses.  相似文献   

Editorial          下载免费PDF全文

J. E. Riviere 《Journal of veterinary pharmacology and therapeutics》2018,41(3):355-355

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Analytical validation of platelet microparticle quantification in cats          下载免费PDF全文

Signe E. Cremer  Jørgen Koch  Nanna Graversen  Anne S. Gravgaard  Rebecca Langhorn  Annemarie T. Kristensen  Jakob L. Willesen  Lise N. Nielsen 《Veterinary clinical pathology / American Society for Veterinary Clinical Pathology》2018,47(3):386-395

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Evaluation of three popular diets fed to pet sugar gliders (Petaurus breviceps): Intake,digestion and nutrient balance          下载免费PDF全文

E. S. Dierenfeld  K. M. Whitehouse‐Tedd 《Journal of animal physiology and animal nutrition》2018,102(1):e193-e208

Three diets fed to 12 pair‐housed sugar gliders, Petaurus breviceps, were evaluated through 5‐day intake and digestion trials following 10‐day transitions. Diets 1 and 2 comprised liquid formula mixes with added vegetables and fruit, and Diet 3 comprised extruded pellets and a liquid formula. Diets eaten contained 16 —19% crude protein, 3%–15% crude fat, 10%–11% neutral detergent fibre, 4%–20% starch and 8%–49% sugar (dry basis). Calculated individual dry matter intakes (DMI) ranged from 3.9 to 5.1 g/day, representing 58.2–78.4 kJ/day. DMI was greater for Diet 2 (7.2% BW) vs. Diet 1 (5.6; p = .006) and Diet 3 (4.2% BW; p = .003). Although these differences were no longer detectable on a MBW basis, animals were shown to have gained BW (+14.2 g; p = .03) on Diet 2. In addition to nutrient composition differing widely among diets, DM digestibility (DMD) was higher in Diet 1 (91.2%) compared to Diet 2 (87.3%; p = .03), but DMD for Diet 3 (88.9%) did not differ from other diets. Gliders demonstrated ability to digest a variety of energy substrates, including simple sugars (96%–99%), fats (81%–96%) and starches (79%–98%), as well as substantial insoluble dietary fibre (58%–75%), with significant difference among diets demonstrated for some nutrients. Animals displayed selective feeding behaviours, rejecting insoluble fibre in produce and preferring the lipid‐coated exterior of pellets. The diets used appeared to be balanced with respect to energy, protein and macromineral content, but may predispose to iron excess, other mineral imbalances (especially Ca deficiency) and obesity—clinical health issues described for pet gliders. Future focus on concentrations, types and utilization of dietary fibre in natural and captive diets, vitamin D metabolism and trace mineral interactions in sugar gliders would assist diet optimization for this highly gummivorous species.  相似文献   

Meta‐analysis of the energy and protein requirements of hair sheep raised in the tropical region of Brazil          下载免费PDF全文

A. P. Oliveira  E. S. Pereira  S. Biffani  A. N. Medeiros  A. M. A. Silva  R. L. Oliveira  M. I. Marcondes 《Journal of animal physiology and animal nutrition》2018,102(1):e52-e60

The objective of this study was to estimate, through mathematical models, energy and protein requirements for maintenance and gain of hair sheep raised in the tropical region of Brazil. To determine the equation parameters, a meta‐analysis of seven independent experiments of nutrient requirements was performed, comprising a total of 243 experimental units (animals), which were conducted under tropical conditions, using hair sheep in growing and finishing phases and endowed of the following quantitative data for each animal: body weight (BW ), empty body weight (EBW ), average daily gain (ADG ), empty body gain (EBG ), heat production (HP ), metabolizable energy intake (MEI ), retained energy (RE ), metabolizable protein intake (MPI ) and body protein content. The regression equations generated were as follows: for Net Energy for maintenance, (NE _m): ; for Net Energy for gain, (NE _g): ; for Metabolizable Protein for maintenance,(MP _m): MPI _(g/day) = 24.8470 (±7.3646) + 560.28 (±99.6582) × EBG _(kg/day); for Net Protein for gain, (NP _g): . The NE _m requirement was 0.246 MJ EBW^?0.75 day^?1. The metabolizable energy for maintenance requirement was 0.391 MJ EBW^?0.75 day^?1. Considering an ADG of 100 g, the NE _g requirement ranged from 0.496 to 1.701 MJ/day for animals with BW ranging from 10 to 40 kg respectively. The efficiencies of use of the metabolizable energy for maintenance and gain were 0.63 and 0.36 respectively. The MP _m requirement was 3.097 g EBW^?0.75 day^?1. Considering an ADG of 100 g, the NP _g requirement ranged from 12.4 to 10.5 g/day for animals with BW ranging from 10 to 40 kg respectively. The total metabolizable energy and protein requirements were lower than those reported by the NRC and AFRC systems. Thus, our results support the hypothesis that nutrient requirements of hair sheep raised in tropical regions differ from wool sheep raised in temperate regions. Therefore, the use of the equations designed in this study is recommended.  相似文献   

Hyperglycaemia in transition dairy cows: Effects of lactational stage and conjugated linoleic acid supplementation on glucose metabolism and turnover          下载免费PDF全文

L. Grossen‐Rösti  E. C. Kessler  A. Tröscher  R. M. Bruckmaier  J. J. Gross 《Journal of animal physiology and animal nutrition》2018,102(2):483-494

Supplementing conjugated linoleic acid ( CLA ) is supposed to spare glucose due to the milk fat‐depressing effect of the trans ‐10, cis ‐12 CLA isomer, and allows repartitioning nutrients despite an energy deficiency in early lactation. However, there is still a lack of knowledge in terms of the dynamic pattern of the glucose turnover in transition dairy cows. We hypothesized that dairy cows supplemented with CLA have an altered rate of glucose turnover and insulin sensitivity during early lactation. We conducted three consecutive hyperglycaemic clamps (HGC ) in weeks ?2, +2 and +4 relative to parturition in Holstein cows supplemented daily either with 70 g of lipid‐encapsulated CLA (6.8 g trans ‐10, cis ‐12 and 6.6 g of the cis ‐9, trans ‐11 CLA isomer; CLA ; n  = 11) or with 56 g of control fat ( CON ; n  = 11). From week ?3 up to week +4 relative to parturition, milk yield and dry matter intake (DMI ) were recorded daily, while body weight (BW ) and milk composition were obtained once weekly. Blood samples were taken once weekly and every 30 min during the HGC . Plasma was analysed for concentrations of glucose, fatty acids (FFA ), beta‐hydroxybutyrate (BHB ), insulin, triglycerides and cholesterol. The CLA supplementation did not affect performance and metabolic parameters except for BHB and cholesterol. Furthermore, insulin concentrations and insulin sensitivity were affected by treatment. During the HGC in early lactation, insulin response was lower and decrease in FFA and BHB greater compared with the HGC in week ?2 although glucose target concentration achieved during the steady‐state period was similar for all three HGC . Our findings in terms of insulin and cholesterol suggest that body reserves are preserved through CLA feeding without restraining animal's performance. Furthermore, CLA effects on cholesterol and triglyceride concentrations indicated beneficial effects on hepatic lipid export contributing to an improved efficiency of prevailing metabolites in circulation.  相似文献