Depletion of dexamethasone in cattle: Food safety study in dairy and beef cattle.

Dexamethasone is approved for cattle in Canada for several conditions, but no withdrawal times are currently provided on the approved labels. Recently, the list of Maximum Residues Limits for Veterinary Drugs in Foods in Canada was amended to include dexamethasone. The objectives of this study were to determine the residue depletion profile of dexamethasone after an extra-label dosage regimen in milk of healthy lactating dairy cattle (n = 18) and in edible tissues of healthy beef cattle (n = 16) and to suggest withdrawal intervals. Dexamethasone was administered intramuscularly at 0.05 mg/kg daily for 3 days. Milk samples were collected prior to treatment and every 12 h up to 96 h post-dose. Muscle, liver, kidney, and peri-renal fat tissues were collected from beef cattle at 3, 7, 11, or 15 days post-dose. Dexamethasone analysis was performed by liquid chromatography/mass spectrophotometry. Dexamethasone residues were detected in milk samples up to 36 h. Muscle and fat had no detectable dexamethasone residues while kidney and liver had detectable residues only on day 3 post-dose. A withdrawal interval of 48 h for milk in Canadian dairy cattle and 7 days for meat in Canadian beef cattle are suggested for the dexamethasone treatment regimen most commonly requested to CgFARAD™.

Pharmacokinetics of combined administration of iron dextran with meloxicam or flunixin meglumine in piglets.

Objective: The objective was to evaluate the pharmacokinetics of compounding non-steroidal anti-inflammatory drugs (NSAIDs) meloxicam or flunixin meglumine with iron dextran (ID) in piglets. Animal: Forty piglets (8 d of age) were randomly allocated into 5 groups (8 piglets/group) and received 1 intramuscular injection in the neck of the following treatments: flunixin meglumine (2.2 mg/kg) administered alone (F) or mixed with ID (F+ID); or meloxicam (0.4 mg/kg) administered alone (M) or mixed with ID (M+ID); or ID alone. Procedure: Blood samples were collected via indwelling jugular catheters at pre-dose, and 10, 20, 30, 45, and 60 min, and 2, 4, 8, 12, 24, 36, 48, and 72 h post-treatment to determine plasma NSAIDs concentrations using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters for plasma meloxicam and flunixin meglumine concentration-time profiles were determined for each piglet using noncompartmental analysis approaches. Statistical analyses were performed using SAS software with significance set at P < 0.05. Results: The AUC0-tlast, AUC0-∞, Cmax, and relative bioavailability values in the M+ID and F+ID groups were lower than corresponding M and F groups. The M+ID group elimination half-life was lower, whereas λz and tmax values were greater than the corresponding M group. Conclusion: Relative bioavailability of meloxicam and flunixin meglumine were reduced when compounded with ID in the same bottle and administered to piglets. Clinical relevance: Further research is warranted to evaluate if decreased NSAID exposure when compounded with ID alters analgesic efficacy or drug residue depletion.

Objectif: L'objectif était d'évaluer la pharmacocinétique de la combinaison d'anti-inflammatoires non stéroïdiens (NSAID) méloxicam ou flunixine méglumine avec du fer dextran (ID) chez les porcelets. Animal: Quarante porcelets (âgés de 8 jours) ont été répartis au hasard en cinq groupes (8 porcelets/groupe) et ont reçu une injection intramusculaire dans le cou des traitements suivants : flunixine méglumine (2,2 mg/kg) administrée seule (F) ou mélangée avec ID (F+ID); soit du méloxicam (0,4 mg/kg) administré seul (M) ou en mélange avec ID (M+ID); ou du ID seul. Procédure: Des échantillons de sang ont été prélevés via des cathéters jugulaires à demeure à la pré-dose, et 10, 20, 30, 45 et 60 min, et 2, 4, 8, 12, 24, 36, 48 et 72 h après le traitement pour déterminer la concentration plasmatique de NSAID par chromatographie liquide-spectrométrie de masse en tandem. Les paramètres pharmacocinétiques des profils concentration-temps du méloxicam et de la flunixine méglumine plasmatiques ont été déterminés pour chaque porcelet à l'aide d'approches d'analyse non compartimentale. Les analyses statistiques ont été effectuées à l'aide du logiciel SAS avec un seuil de signification fixé à P < 0,05. Résultats: Les valeurs AUC0­tlast, AUC0­∞, Cmax et de biodisponibilité relative dans les groupes M+ID et F+ID étaient inférieures à celles des groupes M et F correspondants. La demi-vie d'élimination du groupe M+ID était plus faible, tandis que les valeurs λz et tmax étaient supérieures à celles du groupe M correspondant. Conclusion: La biodisponibilité relative du méloxicam et de la méglumine de flunixine était réduite lorsqu'ils étaient combinés avec ID dans le même flacon et administrés aux porcelets. Pertinence clinique: Des recherches supplémentaires sont nécessaires pour évaluer si une diminution de l'exposition aux NSAID lorsqu'elle est associée à une ID modifie l'efficacité analgésique ou l'épuisement des résidus de médicaments.(Traduit par Dr Serge Messier).

Tissue residue depletion of fenbendazole after oral administration in turkeys.

The objectives of this study were to determine tissue depletion of fenbendazole in turkeys and estimate a withdrawal interval (WDI). Forty-eight 9-week-old turkeys were fed fenbendazole at 30 mg/kg of feed for 7 consecutive days. Three hens and 3 toms were sacrificed every 2 days from 2 to 16 days post-treatment, and tissues were collected to determine fenbendazole sulfone (FBZ-SO2) concentrations using mass spectrometry. At all timepoints, FBZ-SO2 concentrations in liver and skin-adherent fat were above the limit of quantification (1 ppb), with higher concentrations than those in kidney and muscle. Two turkeys had detectable FBZ-SO2 concentrations in kidney at 16 days. No detectable FBZ-SO2 concentrations were found in muscle at 14 and 16 days. Fenbendazole residues depleted very slowly from the liver and a WDI of at least 39 days should be observed under the conditions of this study, in order to comply with Canadian regulatory agencies.

Déplétion du fenbendazole pour les résidus tissulaires après l'administration orale chez les dindons. Les objectifs de cette étude consistaient à déterminer la déplétion du fenbendazole dans les tissus chez les dindons et d'estimer un délai d'attente (DA). Du fenbendazole a été administré à quarante-huit dindons âgés de 9 semaines, à raison de 30 mg/kg d'aliments pendant 7 jours consécutifs. Trois dindes et 3 dindons ont été sacrifiés tous les deux jours pendant les jours 2 à 16 après le traitement et les tissus ont été prélevés pour déterminer les concentrations de fenbendazole sulfone (FBZ-SO2) en utilisant la spectrométrie de masse. À tous les moments de prélèvement, les concentrations de FBZ-SO2 dans le foie et le gras adhérent à la peau étaient supérieures à la limite de quantification (1 ppm), avec des concentrations supérieures à celles présentes dans les reins et les muscles. Deux dindes avaient des concentrations de FBZ-SO2 détectables dans les reins à 16 jours. Aucune concentration détectable de FBZ-SO2 n'a été trouvées dans les muscles à 14 et à 16 jours. Les résidus de fenbendazole se résorbaient très lentement du foie et un DA d'au moins 39 jours devrait être observé conformément aux conditions de cette étude afin de satisfaire aux exigences des agences réglementaires canadiennes.(Traduit par Isabelle Vallières).

Using species distribution models to define nesting habitat of the eastern metapopulation of double-crested cormorants.

When organisms with similar phenotypes have conflicting management and conservation initiatives, approaches are needed to differentiate among subpopulations or discrete groups. For example, the eastern metapopulation of the double-crested cormorant (Phalacrocorax auritus) has a migratory phenotype that is culled because they are viewed as a threat to commercial and natural resources, whereas resident birds are targeted for conservation. Understanding the distinct breeding habitats of resident versus migratory cormorants would aid in identification and management decisions. Here, we use species distribution models (SDM: Maxent) of cormorant nesting habitat to examine the eastern P. auritus metapopulation and the predicted breeding sites of its phenotypes. We then estimate the phenotypic identity of breeding colonies of cormorants where management plans are being developed. We transferred SDMs trained on data from resident bird colonies in Florida and migratory bird colonies in Minnesota to South Carolina in an effort to identify the phenotype of breeding cormorants there based on the local landscape characteristics. Nesting habitat characteristics of cormorant colonies in South Carolina more closely resembled those of the Florida phenotype than those of birds of the Minnesota phenotype. The presence of the resident phenotype in summer suggests that migratory and resident cormorants will co-occur in South Carolina in winter. Thus, there is an opportunity for separate management strategies for the two phenotypes in that state. We found differences in nesting habitat characteristics that could be used to refine management strategies and reduce human conflicts with abundant winter migrants and, at the same time, conserve less common colonies of resident cormorants. The models we use here show potential for advancing the study of geographically overlapping phenotypes with differing conservation and management priorities.

Systemic absorption and adverse ocular and systemic effects after topical ophthalmic administration of 0.1% diclofenac to healthy cats.

OBJECTIVE: To quantify plasma concentrations and determine adverse ocular, renal, or hepatic effects associated with repeated topical ophthalmic application of 0.1% diclofenac to healthy cats. ANIMALS: 8 healthy sexually intact male cats. PROCEDURES: A randomized, placebo-controlled crossover study was conducted. A topical formulation of 0.1% diclofenac was administered 4 times/d for 7 days to 4 cats, and artificial tear (control) solution was administered to the other 4 cats. After a 12-day washout period, cats received the other treatment. Ophthalmic examinations were performed daily. Plasma samples were obtained on days 1 and 7 for pharmacokinetic analysis. A CBC, serum biochemical analysis, urinalysis, determination of urine protein-to-creatinine ratio, and determination of glomerular filtration rate were performed before the start of the study and after each 7-day treatment period. RESULTS: Mild conjunctival hyperemia was the only adverse ocular effect detected. Maximal drug concentration and area under the curve were significantly higher on day 7 than on day 1. Diclofenac-treated cats had a significantly lower glomerular filtration rate than did control-treated cats after the second but not after the first treatment period, presumably associated with iatrogenic hypovolemia. CONCLUSIONS AND CLINICAL RELEVANCE: Topical ophthalmic administration of 0.1% diclofenac was well tolerated in healthy cats, with only mild signs of ocular irritation. Detectable systemic concentrations of diclofenac were achieved with accumulation over 7 days. Systemic absorption of diclofenac may be associated with reduced glomerular filtration rate, particularly in volume-contracted animals. Topical ophthalmic 0.1% diclofenac should be used with caution in volume-contracted or systemically ill cats.

Intra-articular pharmacokinetics of a gentamicin impregnated collagen sponge in the canine stifle: an experimental study.

OBJECTIVE: To investigate local and systemic pharmacokinetics of gentamicin after intra-articular implantation of a gentamicin impregnated collagen sponge (GICS) in the inflamed canine joint. STUDY DESIGN: Descriptive repeated measures experimental study. ANIMALS: Dogs (n = 9). METHODS: Stifle joint inflammation was caused by urate injection. Twenty-four hours later a GICS (gentamicin dose, 6 mg/kg) was arthroscopically implanted. Synovial fluid and plasma gentamicin concentrations were measured for 14 days after implantation, and pharmacokinetic parameters modeled using statistical moment analyses. RESULTS: Intra-articular gentamicin concentrations fell to sub-MIC for Staphylococcus sp. (4 µg/mL) by 22.4 hours (95% CI: 18.6-26.2) after sponge implantation. Cmax synovial was 2397 µg/mL (95%CI: 1161-3634 µg/mL) at 1.2 hours (95%CI: 0.5-1.8 hours). Plasma gentamicin concentrations achieved levels of Cmax plasma = 8.0 µg/mL (95%CI: 6.1-10.0 µg/mL) at 1.5 hours (95%CI: 0.8-2.1) after GICS placement and fell below target trough of 2.0 µg/mL by 5.6 hours (95%CI: 4.7-6.5 hours) after GICS placement. CONCLUSIONS: Intra-articular gentamicin concentration after GICS placement at an IV-equivalent dose reached high levels and declined rapidly. The maximum plasma levels attained were ∼1/3 of the recommended sub-toxic target for people after parenteral gentamicin administration.

Cardiopulmonary effects of intravenous fentanyl infusion in dogs during isoflurane anesthesia and with concurrent acepromazine or dexmedetomidine administration during anesthetic recovery.

OBJECTIVE: To evaluate the cardiopulmonary effects of IV fentanyl administration in dogs during isoflurane anesthesia and during anesthetic recovery with or without dexmedetomidine or acepromazine. ANIMALS: 7 sexually intact male purpose-bred hound-type dogs aged 11 to 12 months. PROCEDURES: Dogs received a loading dose of fentanyl (5 µg/kg, IV) followed by an IV infusion (5 µg/kg/h) for 120 minutes while anesthetized with isoflurane and for an additional 60 minutes after anesthesia was discontinued. Dogs were randomly assigned in a crossover design to receive dexmedetomidine (2.5 µg/kg), acepromazine (0.05 mg/kg), or saline (0.9% NaCl) solution (1 mL) IV after anesthesia ceased. Cardiopulmonary data were obtained during anesthesia and for 90 minutes after treatment administration during anesthetic recovery. RESULTS: Concurrent administration of fentanyl and isoflurane resulted in significant decreases in mean arterial blood pressure, heart rate, and cardiac index and a significant increase in Paco2. All but Paco2 returned to pretreatment values before isoflurane anesthesia was discontinued. During recovery, dexmedetomidine administration resulted in significant decreases in heart rate, cardiac index, and mixed venous oxygen tension and a significant increase in arterial blood pressure, compared with values for saline solution and acepromazine treatments. Acepromazine administration resulted in significantly lower blood pressure and higher cardiac index and Po2 in mixed venous blood than did the other treatments. Dexmedetomidine treatment resulted in significantly lower values for Pao2 and arterial pH and higher Paco2 values than both other treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl resulted in transient pronounced cardiorespiratory effects when administered during isoflurane anesthesia. During anesthetic recovery, when administered concurrently with an IV fentanyl infusion, dexmedetomidine resulted in evidence of cardiopulmonary compromise and acepromazine transiently improved cardiopulmonary performance.

Effects of injectable anesthetic combinations on left ventricular function and cardiac morphology in Sprague-Dawley rats.

Novel anesthetic agents or combinations may provide superior general anesthesia for echocardiography in rodents with the potential for reduced adverse effects. This study sought to characterize the effects of 3 injectable anesthetics on left ventricular (LV) systolic function and cardiac morphology in healthy male and female rats. Rats underwent echocardiographic assessment after general anesthesia via pentobarbital or combinations of ketamine and medetomidine (KME) and ketamine and midazolam (KMI) according to a crossover Latin-square design. Blood samples for serum estradiol measurements were obtained from all females after echocardiography with each anesthetic. Rats given KMI showed superior LV systolic function with the highest values for fractional shortening (FS), ejection fraction (EF) and stroke volume, whereas heart rate was greatest with pentobarbital, followed by KMI and then KME. KME produced the greatest effects on cardiac morphology, most notably during systole, including reduced septal and posterior wall thickness and increased LV chamber dimensions and volumes. In addition, KME had the greatest cardiac-depressing effects on LV systolic function, including reduced FS, EF, and heart rate values. Compared with male rats, female rats had superior LV function with greater EF and FS values, whereas male rats showed higher heart rate. Significant negative correlations were noted between serum estradiol levels and FS and EF values in female rats receiving KME. We conclude that the combination of KMI may be a superior anesthetic for use in male and female rats undergoing echocardiography.

Weekend bias in Citizen Science data reporting: implications for phenology studies.

Studies of bird phenology can help elucidate the effects of climate change on wildlife species but observations over broad spatial scales are difficult without a network of observers. Recently, networks of citizen volunteers have begun to report first arrival dates for many migratory species. Potential benefits are substantial (e.g., understanding ecological processes at broad spatial and temporal scales) if known biases of citizen data reporting are identified and addressed. One potential source of bias in bird phenology studies is the tendency for more "first" migratory arrivals to be reported on weekends than on weekdays. We investigated weekend bias in data reporting for five common bird species in North America (Baltimore Oriole, Icterus galbula; Barn Swallow, Hirundo rustica; Chimney Swift, Chaetura pelagica; Purple Martin, Progne subis; and Ruby-throated Hummingbird, Archilochus colubris), and assessed whether this bias affected mean arrival dates reported using data from historical (1880-1969; N = 25,555) and recent (1997-2010; N = 63,149) Citizen Science databases. We found a greater percentage of first arrivals reported on weekends and small but significant differences in mean arrival dates (approximately 0.5 days) for four of five species. Comparing time periods, this weekend bias decreased from 33.7 % and five species in the historical time period to 32 % and three species in the recent, perhaps related to changes in human activity patterns. Our results indicate that weekend bias in citizen data reporting is decreasing over time in North America and including a 'day of week' term in models examining changes in phenology could help make conclusions more robust.

A comparison of 3 anesthetic protocols for 24 hours of mechanical ventilation in cats.

OBJECTIVE: To compare the recovery times, recovery quality, and cardiovascular (CV) effects of 3 anesthetic protocols during 24 hours of mechanical ventilation (MV) in healthy cats. DESIGN: Prospective, randomized, crossover study. SETTING: Research laboratory at a veterinary teaching hospital. ANIMALS: Six healthy intact male purpose-bred cats. INTERVENTIONS: Each cat was randomly assigned to receive 3 anesthetic protocols for 24 hours of MV; Protocol K consisted of ketamine, Protocol P, propofol; and Protocol PK, propofol plus fixed-rate low-dose ketamine. Each infusion drug dose was adjusted using a sedation scoring system. All protocols included fixed doses of fentanyl (10 µg/kg/h) and midazolam (0.5 mg/kg/h). MEASUREMENTS AND MAIN RESULTS: Drug doses and recovery times were recorded. Recovery quality was scored. Blood gas results, CV parameters, and frequency of bradycardia or hypotension requiring interventions were recorded. The mean d dose ± standard error of K was 81.3 ± 3.3 µg/kg/m. The median dose (95% cardiac index) of propofol (µg/kg/m) in PK was 16.0 (13.1, 19.6) and in P was 48.1 (39.3, 58.9). P necessitated significantly more propofol than PK (P < 0.05). Protocol K (35.6 ± 3.2 hours) had significantly longer times to full recovery compared to P (18.2 ± 3.2 hours). Protocol K had significantly longer times to head up, crawling, and standing compared to P and PK. Cats sedated with PK (2.33 ± 0.47) required significantly more interventions for hypotension than K (0.50 ± 0.47). Protocol P (3.2 ± 0.4) and PK (1.4 ± 0.3) required significantly more interventions for bradycardia compared to K (0.8 ± 0.3). When comparing protocol K to P and PK, significant differences in blood pressure, lactate, oxygen delivery, and oxygen consumption were noted. CONCLUSIONS: Cats anesthetized with P had shorter times to full recovery compared to K. Cats anesthetized with K required fewer interventions for bradycardia or hypotension but had longer recovery times compared to P or PK. Protocol PK reduced the propofol dose required to maintain optimal anesthesia.