Studies on itraconazole delivery and pharmacokinetics in mallard ducks (Anas platyrhynchos)

Avian aspergillosis is commonly treated with itraconazole (ITZ). This paper describes two studies using mallard ducks (Anas platyrhynchos). The first study evaluated in vivo release of ITZ from subcutaneously injected controlled-release gel formulations and the second study compared pharmacokinetic parameters for two ITZ oral suspensions. ITZ-A suspension was prepared by mixing contents of commercially available capsules with hydrochloric acid and orange juice. ITZ-B suspension was prepared by dispersing the complex of the drug with hydroxypropyl-beta-cyclodextrin in water. Concentrations of ITZ and its active metabolite, hydroxyitraconazole (OH-ITZ), in plasma and tissue samples were measured using high-performance liquid chromatography. In the second study, drug concentrations in plasma samples were also analyzed using a bioassay. After administration of two ITZ controlled-release formulations, plasma and tissue concentrations of ITZ and OH-ITZ were either very low (< or = 52 ng/mL) or undetectable. Exceptions included skin, subcutaneous fat, and muscle adjacent to the injection site. The drug from ITZ-A and ITZ-B suspensions was absorbed after oral administration. ITZ pharmacokinetic parameters for both suspensions in mallard ducks were similar and the bioassay successfully measured ITZ equivalents in plasma samples from ducks.     

Carbofuran poisoning in mallard ducks

Carbofurane, a pesticide from the group of carbamates, has been employed against soil nematodes on a small meadow at the lake of Lugano, Switzerland. On the next morning, the first cases of death involving a total of 19 mallard ducks (Anas platyrhynchos) have been reported. By inhibiting the enzymatic breakdown of the neurotransmitter acetycholine, carbamates lead to excessive activation of the parasympathicus. In addition, paralysis of skeletal muscles is caused by continued stimulation of neuromuscular junctions. Death may occur by asphyxia. In the present case report, the diagnosis of poisoning could be confirmed by the chemical detection of carbofuran in the stomach, blood, muscle and kidney tissue of the affected mallard ducks.     

Lectin binding patterns in the olfactory bulb of mallard ducks (Anas platyrhynchos)

We histologically examined lectin binding patterns in the olfactory bulb of mallard ducks (Anas platyrhynchos) using 21 biotinylated lectins. Positive staining for the N‐acetylglucosamine‐specific lectins (Bandeiraea simplicifolia II, Datura stramonium, Lycopersicon esculentum, Solanum tuberosum, Triticum vulgare), galactose or N‐acetylgalactosamine‐specific lectins (Artocarpus intergrifolia, Phaseolus vulgaris erythroagglutinin, Phaseolus vulgaris leucoagglutinin, Ricus communis) and the mannose‐specific lectins (Lens culinaris and Pisum sativum) was observed in the olfactory nerve and glomerular layers. Canavalia ensiformis staining showed a similar pattern to that obtained with the lectins and there was also faint staining in the mitral cells. Olfactory nerve axons terminate in the glomeruli, where they make excitatory synapses with the dendrites of mitral cells. This finding indicates that glycoconjugates that bind Canavalia ensiformis play an important role in formation of glomeruli. No positive staining for the other lectins was seen in the olfactory bulb. Based on these results, we conclude that cell surface sugar moieties of the olfactory bulb in mallard ducks express N‐acetylglucosamine and mannose residues rather than N‐acetylgalactosamine residues. The carbohydrate composition of mallard duck olfactory bulb differed from that of other vertebrates found in previous studies.     

Pharmacodynamics of flunixin and ketoprofen in mallard ducks (Anas platyrhynchos).

Flunixin (FLX) and ketoprofen (KET) are potent nonsteroidal anti-inflammatory drugs (NSAIDs) used to alleviate pain and decrease inflammation. These drugs block access of arachidonic acid to its binding site on the cyclooxygenase enzyme, thus preventing conversion to thromboxane A2 and subsequent degradation to thromboxane B2 (TBX). Consequently, plasma TBX may be used to estimate duration of NSAID action. Sixteen adult mallard ducks (Anas platyrhynchos) were randomly assigned to three treatment groups: control (n = 4), FLX 5 mg/kg (n = 6), or KET 5 mg/kg (n = 6). Blood samples were taken 1 hr prior to and just before (0 hr) injection and 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, and 48 hr after injection. Plasma samples were analyzed for corticosterone and TBX. The feces were tested for the presence of hemoglobin and the ducks were euthanized for complete necropsy at the end of the study. Samples of muscle, kidney, liver, proventriculus, and intestine were taken for histologic analysis. Thromboxane was suppressed significantly in all birds following administration of either FLX or KET for 4 hr and decreased for approximately 12 hr compared with baseline samples (-1 and 0 hr). In the control group, TBX gradually declined over time. None of the ducks showed evidence of gastrointestinal bleeding, but the FLX group had muscle necrosis present at injection sites. FLX and KET likely exert pharmacological effects for at least 12 h. Although degree of TBX inhibition cannot be correlated absolutely with degree of analgesia or anti-inflammatory effects, it is possible that these effects are present during this time. This work suggests that FLX and KET can potentially be used as anti-inflammatory and analgesic agents in waterfowl. However, because of muscle necrosis at the injection site, we do not recommend parenteral use of FLX in ducks.     

Comparison of fluid types for resuscitation after acute blood loss in mallard ducks (Anas platyrhynchos)

Objective – The purpose of this study was to determine the LD₅₀ for acute blood loss in mallard ducks ( Anas platyrhynchos ), compare the mortality rate among 3 fluid resuscitation groups, and determine the time required for a regenerative RBC response.
Design – Prospective study.
Setting – Medical College of Wisconsin Research facility.
Animals – Eighteen mallard ducks were included for the LD₅₀ study and 28 for the fluid resuscitation study.
Interventions – Phlebotomy was performed during both the LD₅₀ and fluid resuscitation studies. Ducks in the fluid resuscitation study received a 5 mL/kg intravenous bolus of crystalloids, hetastarch (HES), or a hemoglobin-based oxygen-carrying solution (HBOCS).
Measurements and Main Results – The LD₅₀ for acute blood loss was 60% of total blood volume. This blood volume was removed in the fluid resuscitation study to create a model of acute blood loss. Following fluid administration, 6 birds in the crystalloid group (66%), 4 birds in the HES group (40%), and 2 birds in the HBOCS group (20%) died. No statistical difference in mortality rate was seen among the 3 fluid resuscitation groups. Relative polychromasia evaluated post-phlebotomy demonstrated regeneration starting at 24 hours and continuing through 48 hours.
Conclusions – The LD₅₀ for acute blood loss in mallard ducks was 60% of their total blood volume. Although no statistical difference in mortality rate was appreciated among the 3 fluid resuscitation groups, a trend of decreased mortality rate was observed in the HBOCS group. An early regenerative response was apparent following acute blood loss.     

Pharmacokinetics and pharmacodynamics of alfaxalone after a single intramuscular or intravascular injection in mallard ducks (Anas platyrhynchos)

Pharmacokinetics and pharmacodynamics of alfaxalone was performed in mallard ducks (Anas platyrhynchos) after single bolus injections of 10 mg/kg administered intramuscularly (IM; n = 10) or intravenously (IV; n = 10), in a randomized cross‐over design with a washout period between doses. Mean (±SD) C_max following IM injection was 1.6 (±0.8) µg/ml with T_max at 15.0 (±10.5) min. Area under the curve (AUC) was 84.66 and 104.58 min*mg/ml following IV and IM administration, respectively. Volume of distribution (V_D) after IV dose was 3.0 L/kg. The mean plasma clearance after 10 mg/kg IV was 139.5 (±67.9) ml min^?1 kg^?1. Elimination half‐lives (mean [±SD]) were 15.0 and 16.1 (±3.0) min following IV and IM administration, respectively. Mean bioavailability at 10 mg/kg IM was 108.6%. None of the ducks achieved a sufficient anesthetic depth for invasive procedures, such as surgery, to be performed. Heart and respiratory rates measured after administration remained stable, but many ducks were hyperexcitable during recovery. Based on sedation levels and duration, alfaxalone administered at dosages of 10 mg/kg IV or IM in mallard ducks does not induce clinically acceptable anesthesia.     

Pathogenesis of lead shot poisoning in the mallard duck.

Adult mallard ducks were administered steel pellets to determine the rate of excretion from the gastrointestinal tract. In separate studies the ducks were administered 5 number 6 lead pellets. Birds were examined for clinical signs and sacrificed at given intervals over a 20 day period to assess changes in tissue structure and concentrations of lead with time. The above studies were conducted in 2 groups of ducks, fed a low or a high fiber diet. The rate of steel pellet excretion on birds on the low fiber diet decreased with an increase in pellet size. Pellet excretion was greatly reduced in birds fed the high fiber diet. Administration of lead shot resulted in the development of green diarrhea, anorexia and weakness. It also produced high concentrations of lead in the blood, kidney, liver and bone with lower concentrations in skeletal muscle. The major lesions were destruction of the mitotically active proventricular epithelium and medullary osteocytes, destruction of pectoral muscle cells and the presence of intranuclear inclusion bodies in the proximal tubular epithelium of the kidneys. Birds on the high fiber diet demonstrated more severe clinical signs and higher concentrations of lead in the tissues.     

Subacute toxic effects of dietary T-2 toxin in young mallard ducks.

Young Mallard ducks (Anas platyrhynchos) were fed diets containing purified T-2 toxin at levels of 20 or 30 ppm for two or three weeks. Ingestion of T-2 toxin was associated with reduced weight gain and delayed development of adult plumage. Affected ducks developed caseonecrotic plaques throughout the upper alimentary tract, especially in oropharynx and ventriculus. Several ducks also developed severe ulcerative, proliferative esophagitis and proventriculitis. Generalized atrophy of all lymphoid tissues consistently occurred. The manifestations of T-2 mycotoxicosis in Mallard ducks were mostly attributable to irritant toxicity to the alimentary mucosa. The T-2 toxin caused neither hematopoietic suppression nor a hemorrhagic syndrome in ducks. These alimentary lesions of T-2 mycotoxicosis in ducks do not resemble diseases of native waterfowl presently being recognized in routine surveillance of waterfowl mortality in Saskatchewan.     

Pasteurella multocida-associated sinusitis in khaki Campbell ducks (Anas platyrhynchos)

Pasteurella multocida group B, serotype 3, was isolated from sinusitis-affected khaki Campbell ducks. To study the role of P. multocida in sinusitis, commercial khaki Campbell ducks were experimentally infected with P. multocida alone or combined with Escherichia coli. In Expt. 1, experimental ducks were infected with P. multocida intranasally or ocularly. A comparison was done by intranasal inoculation with pooled nasal discharge from the affected ducks or phosphate-buffered saline. The ducks intranasally inoculated with the nasal discharge or P. multocida showed sinusitis. In Expt. 2, E. coli alone or a combination of P. multocida and E. coli was intranasally inoculated into experimental ducks. The ducks intranasally inoculated with the combination of P. multocida and E. coli had sinusitis, the same as found in the field but less severe than that of the field cases. Pasteurella multocida was already present in litter/floor of duck farms. We concluded that P. multocida played a role in induction of sinusitis. However, the sinusitis in ducks may be initiated by poor management, especially in the brooding period of ducks.     

Histological aspects of the syrinx of the male mallard (Anas platyrhynchos)

The syrinx of the duck is characterized by a conspicious sexual dimorphism. In the male mallard, a large osseous bulla is present on the left syringeal side. The present work describes the structures of the male syrinx, which were studied by means of histochemistry, immunohistochemistry and electron microscope. In the right distal tympanum a caudally oriented, protruding structure was observed, which was identified as the valvula syringealis. The syringeal structures like valvula, tympanum, bulla, pessulus and the bronchi were in general covered by a respiratory epithelium, however, local modifications in cellular height and numbers of ciliated and goblet cells were observed. The presence of intrinsic musculature was confirmed by means of immunohistochemistry. Smooth muscle cells reaching from the lateral parts of the inter-bronchial ligament to the medial line and cranially to the inner tympaniform membranes were demonstrated. We suppose that these muscle cells play a role in syringeal sound generation by influencing the tension of the medial tympaniform membranes.     

Susceptibility of Muscovy (Cairina Moschata) and mallard ducks (Anas Platyrhynchos) to experimental infections by different genotypes of H5N1 avian influenza viruses

It is a fact that in Viet Nam, Muscovy ducks are raised in large populations (approximately 8 million), usually kept in small flocks together with mallards and chickens. As a result, it is a great concern for epidemiologists to elucidate possible differences in relation to these species being exposed to infection with H5N1. To do this, an experimental study on infections with different genotypes of H5N1 in mallards and Muscovy ducks have been conducted, where it was found that the mortality of the inoculated Muscovy ducks was at least 80%, regardless of the virus strain employed. In contrast, the mortality of the mallards ranged from nil to 100%, which suggests that Muscovy ducks are more susceptible to HPAIV H5N1 infection in terms of disease development and mortality. It was also found that higher virus titers developed in vital organs of Muscovy ducks compared to mallards, particularly in the brain. Due to their high susceptibility, it is unlikely that Muscovy ducks act as a silent reservoir. The virus strains used in this study, to a certain degree, differed in their virulence properties to the bird species in question.     

Carboplatin for treatment of a Sertoli cell tumor in a mallard (Anas platyrhynchos)

A 13‐year‐old male mallard was diagnosed with a non‐resectable Sertoli cell tumor involving the left testis. The duck was treated with four doses of single‐agent carboplatin given at 4‐ to 5‐week intervals. Heteropenia, 2 weeks after each treatment, was the acute dose‐limiting toxicity. The tumor reduced in size by 25%, and the duck's clinical condition improved for 12 months. Sertoli cell tumors are rare in birds, and this is the first report, to our knowledge, of attempted chemotherapy treatment in the veterinary literature.     

The syrinx of the male mallard (Anas platyrhynchos): special anatomical features

The aim of this study was to investigate the special anatomical and topographical features of the syrinx in male adult stock ducks (Anas platyrhynchos). The syrinx of the mallard is a tracheobronchial type, consisting of a tympanum, a pessulus, medial tympaniform membranes, interanular membranes, an interbronchial ligament (bronchidesmus), and bronchosyringeal cartilage semi-rings. Using a frozen sagittal section, it was possible to document the syringeal valve at the right lateral side of the tympanum. In the male stock duck the pessulus was massive and showed a longish oval, transparent area ventrally. The middle part of the pessulus had a nose-shaped process on its left side, on which the left medial tympaniform membrane originated. The left-sided, pear-shaped syringeal bulla was divided into a left major and right minor chamber by a double-walled, semilunar and opaque septum, approximately 5-6 mm in height. The first left and right C-shaped bronchosyringeal cartilage was more prominent than the other ones and showed partial ossification. In addition, the first left bronchosyringeal cartilage was obviously thicker than the right one. In conclusion, it can be stated that the syrinx in male adult mallards shows some notable specific anatomical features that might have an influence on vocalization. However, to understand the complex mechanism of vocalization in mallards, more investigations, especially obtained by sonography and endoscopy, will be needed.     

Pharmacokinetics of chloramphenicol in Chinese spot-billed ducks (Anas poecilorhyncha)*

The pharmacokinetic behavior of chloramphenicol in Chinese spot-billed ducks (Anas poecilorhyncha) was investigated. Single doses of chloramphenicol were given by the intravenous (22 mg/kg), intramuscular (22 mg/kg), and oral route (55 mg/kg) to six, seven and six ducks, respectively. Serum samples were collected at various times and analyzed for chloramphenicol by a radio-enzymatic procedure. The time—concentration curves after intravenous administration were described by one-compartment kinetics. The mean half-lives for the intravenous, intramuscular, and oral route were 102.5, 104.5 and 151.4 min, respectively. There was little individual variation in the time—concentration plots for either the intravenous or intramuscular route. However, following oral administration, there was considerable individual variation indicating erratic absorption. From the intravenously derived, pharmacokinetic parameters, dosage regimens applicable to either the intravenous or intramuscular route, were developed.