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).

Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves.

OBJECTIVE: To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. ANIMALS: 25 calves. PROCEDURES: A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. RESULTS: At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.

Cardiopulmonary effects of anesthetic induction with thiopental, propofol, or a combination of ketamine hydrochloride and diazepam in dogs sedated with a combination of medetomidine and hydromorphone.

OBJECTIVE: To evaluate the cardiopulmonary effects of anesthetic induction with thiopental, propofol, or ketamine hydrochloride and diazepam in dogs sedated with medetomidine and hydromorphone. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs received 3 induction regimens in a randomized crossover study. Twenty minutes after sedation with medetomidine (10 microg/kg, IV) and hydromorphone (0.05 mg/kg, IV), anesthesia was induced with ketamine-diazepam, propofol, or thiopental and then maintained with isoflurane in oxygen. Measurements were obtained prior to sedation (baseline), 10 minutes after administration of preanesthetic medications, after induction before receiving oxygen, and after the start of isoflurane-oxygen administration. RESULTS: Doses required for induction were 1.25 mg of ketamine/kg with 0.0625 mg of diazepam/kg, 1 mg of propofol/kg, and 2.5 mg of thiopental/kg. After administration of preanesthetic medications, heart rate (HR), cardiac index, and PaO(2) values were significantly lower and mean arterial blood pressure, central venous pressure, and PaCO(2) values were significantly higher than baseline values for all regimens. After induction of anesthesia, compared with postsedation values, HR was greater for ketamine-diazepam and thiopental regimens, whereas PaCO(2) tension was greater and stroke index values were lower for all regimens. After induction, PaO(2) values were significantly lower and HR and cardiac index values significantly higher for the ketamine-diazepam regimen, compared with values for the propofol and thiopental regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine and hydromorphone caused dramatic hemodynamic alterations, and at the doses used, the 3 induction regimens did not induce important additional cardiovascular alterations. However, administration of supplemental oxygen is recommended.

Effects of a peripheral alpha2 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs.

OBJECTIVE: To evaluate the effects of administration of a peripheral alpha(2)-adrenergic receptor antagonist (L-659,066), with and without concurrent administration of glycopyrrolate, on cardiopulmonary effects of medetomidine administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs received saline (0.9% NaCl) solution (saline group), L-659,066 (group L), or L-659,066 with glycopyrrolate (group LG). These pretreatments were followed 10 minutes later by administration of medetomidine in a randomized crossover study. Hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained prior to pretreatment, 5 minutes after pretreatment, and after medetomidine administration at intervals up to 60 minutes. RESULTS: After pretreatment in the L and LG groups, heart rate, cardiac index, and partial pressure of oxygen in mixed-venous blood (PvO2) values were higher than those in the saline group. After medetomidine administration, heart rate, cardiac index, and PvO2 were higher and systemic vascular resistance, mean arterial blood pressure, and central venous pressure were lower in the L and LG groups than in the saline group. When the L and LG groups were compared, heart rate was greater at 5 minutes after medetomidine administration, mean arterial blood pressure was greater at 5 and 15 minutes after medetomidine administration, and central venous pressure was lower during the 60-minute period after medetomidine administration in the LG group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L-659,066 prior to administration of medetomidine reduced medetomidine-induced cardiovascular changes in healthy dogs. No advantage was detected with concurrent administration of L-659,066 and glycopyrrolate.