ABSENCE OF ACUTE TOXICITY OF A SINGLE INTRAMUSCULAR INJECTION OF MELOXICAM IN GOLDFISH ( CARASSIUS AURATUS AURATUS): A RANDOMIZED CONTROLLED TRIAL.

Meloxicam is a nonsteroidal anti-inflammatory drug with preferential cyclooxygenase-2 inhibitory activity. It is frequently used in veterinary medicine, including in fish species. The efficacy and safety of meloxicam, however, has not yet been reported in adult fish. The purpose of this study was to evaluate the acute toxicity of a single intramuscular injection of meloxicam in goldfish ( Carassius auratus auratus). Following 3 wk of acclimation, 32 goldfish were randomly assigned to two groups of 16 individuals. Fish from the treatment group received a single intramuscular injection of 5 mg/kg meloxicam, while the fish from the control group received a single intramuscular injection of a 0.9% sodium chloride solution using a similar volume (1 ml/kg). No external lesions, mortality, or modifications in behavior or position in the water column were noted during the following 72 hr. Three days after the initial injection, all fish were euthanized by immersion in a solution of tricaine methanesulfonate. Complete postmortem and histologic evaluations were performed for each fish. Hemorrhage and muscular necrosis were observed at the site of injection in fish from both groups. Multiple granulomas of undetermined etiology were detected in numerous organs from fish of both groups. No statistically significant differences were detected in regard to the lesions observed in these two groups. This study demonstrates that a single intramuscular injection of meloxicam at a dosage of 5 mg/kg does not cause acute toxicity in goldfish.

Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon).

OBJECTIVE: To assess the population pharmacokinetics of methadone in deer. STUDY DESIGN: Prospective non-randomized experimental trial. ANIMALS: Twelve healthy adult sika deer (nine males and three females). METHODS: Deer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg(-1) or 1 mg kg(-1) . Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM). RESULTS: A two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour(-1) ), metabolic clearance (34.6 L hour(-1) ), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour(-1) ), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour(-1) , 121.0 L hour (-1) , 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration. CONCLUSIONS AND CLINICAL RELEVANCE: Following intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer.

Fatal Aspergillus flavus rhinitis with gastrointestinal gaseous distension in a Cape porcupine.

An adult female Cape porcupine (Hystrix africaeaustralis) was presented because of marked abdominal distension, acute dyspnea, and lethargy. Physical examination and standard radiographs revealed marked and diffuse gaseous dilation of the stomach and intestines of undetermined origin. The porcupine died despite medical therapy and surgical intervention. Postmortem examination revealed chronic fungal (Aspergillus flavus) rhinitis. Given that rodents are obligate nasal breathers, the rhinitis likely resulted in substantial upper airway obstruction leading to aerophagia.

Resting breathing frequency in aquatic mammals: a comparative analysis with terrestrial species.

Several species of aquatic mammals, while resting at the water surface, breathe with a low frequency (f). We asked if this was a general characteristic of mammals adapted to life in water. Measurements of f were obtained in 42 aquatic mammals of 19 species, during resting conditions. Data of additional 10 species were available from the literature. The allometric function for aquatic mammals was f=33W(-0.42) (f, breaths/min; W, kg; N=29, one data point per species, from six mammalian orders). This exponent was significantly different from that of the allometric curve of terrestrial mammals (W(-0.25)). The difference between aquatic and terrestrial species was small up to about 10kg, and widened with the increase in W. Out of several possibilities, it seems that the breath-holding response to favour buoyancy at the water surface could have contributed to the evolution of the low-f breathing, but a satisfactory explanation for the allometric pattern of f is still unavailable. In semi-aquatic mammals the low-f pattern observed at the water surface was maintained ashore, with no difference in the allometric function. As in the adult, also in the newborn of aquatic species f was low, compared to same-size neonates of terrestrial species. Hence, the low f has evolved to be part of the genetic makeup of aquatic mammals, retained when the animal is ashore, and already expressed at birth.